Zlatko Dalic's side actually started on the front foot but were made to pay for three missed chances when midfielder Saul Niguez headed Spain into a 24th-minute lead.
Marco Asensio was the star of the show with a goal and four assists, one of which was his own shot which dropped over the line after hitting goalkeeper Lovre Kalinic on the head on its way down from the crossbar.
The hosts were three up at half time and five up before the hour mark as Rodrigo and Sergio Ramos got in on the act, and Isco rounded off the scoring on a humbling night for this summer's beaten finalists in Russia.
Relive the action from the Estadio Martinez Valero with Sports Mole's minute-by-minute updates below.
6.45pmSpain and Croatia have each beaten England in the Three Lions' last two international fixtures, and tonight two of the most star-studded squads in world football face off in a UEFA Nations League A game at the Estadio Martinez Valero. Sports Mole have every kick covered with our minute-by-minute updates.
6.51pmSpain boss Luis Enrique seems well suited to international management. The modern-day tinkerman rotated his Barcelona side for 19 consecutive La Liga matches in his debut season and freshens this XI with three changes from Saturday's 2-1 win over England.
6.53pmMarcos Alonso drops out for Valencia's Jose Luis Gaya who makes his senior bow after 34 caps for the Spanish youth teams. Alonso's Chelsea teammates Cesar Azpilicueta and Alvaro Morata miss out, although Blues won't be complaining ahead of the resumption of the Premier League season on Saturday.
6.55pmEnrique's other changes see Dani Ceballas and Marco Asensio come in for Thiago Alcantara and Iago Aspas, which means that six of the starting XI play their club football for Real Madrid.
6.57pmHaving scored what turned out to be the winning goal at Wembley, converted striker Rodrigo gets the chance to make the number nine spot his own with another start. Although Diego Costa will be gunning for his place back having opted out of these fixtures due to personal reasons.
6.59pmThis is Croatia's first competitive game since the World Cup final, although they did have a friendly with Portugal on Thursday which ended in a 1-1 draw. Manager Zlatko Dalic only names five of the team which began July's defeat to France in Moscow as he gives a couple of fringe players a go.
7.01pmJourneyman striker Ivan Santini is one of those to benefit from Dalic's rotation. The ex-Caen and Freiburg man has been rewarded for his fast start to life at Anderlecht with a third cap this evening. Lovre Kalinic, who also played his football in Belgium for Gent, starts in goal following Danijel Subasic's retirement.
7.01pmJourneyman striker Ivan Santini is one of those to benefit from Dalic's rotation. The ex-Caen and Freiburg forward is rewarded for his fast start to life at Anderlecht with a third cap this evening. Lovre Kalinic, who also plays in Belgium for Gent, starts in goal following Danijel Subasic's retirement.
7.03pmCroatia's class is in midfield where Luka Modric, Ivan Rakitic, Mateo Kovacic and Marcelo Brozovic all start in a midfield diamond. Barcelona midfielder Rakitic wins his 100th international cap tonight, making him the eighth player to reach that milestone, following fellow maestro Modric.
7.05pmIvan Perisic was probably Croatia's biggest attacking threat during the World Cup and he will be tasked with supporting lone striker Santini. The Inter Milan winger has 22 goals in 74 caps and was linked with Manchester United in the summer but seems destined to avoid the Premier League all his career.
7.07pmOn loan Chelsea midfielder Kovacic is the only Premier League representative in the Croatia XI, which is a bit of a surprise considering that English football has been rich with Croats in recent years. Liverpool defender Dejan Lovren did not make the squad as he continues to recover from injury.
7.09pmWhile Croatia are a growing force, Spain were the dominant side in international football from 2008 until their dethroning as world champions in 2014, but this team is now in a rebuilding phase and is adapting to a new high-press, high-intensity approach that is Luis Enrique's mantra, as seen at Wembley.
7.11pmThere are now very few survivors from that famous Vicente del Bosque side which won three successive major tournaments either side of the turn of the decade. Of tonight's starters, only Sergio Ramos and Sergio Busquets have lifted international silverware so there should be a new hunger to this team.
7.13pmSpeaking of Ramos, he is one of nine Spaniards who were shortlisted for the FIFPro World XI 2018 when the nominees were announced earlier this week. Having captained Real Madrid to a third straight Champions League triumph, the 32-year-old seems certain to make the final cut.
7.15pmSpain's other nominees were David de Gea, Jordi Alba, Gerard Pique, Dani Carvajal, Sergio Busquets, Andreas Iniesta, David Silva, and Isco. The fact that three of those players have retired from international football further illustrates that this is a new era that Enrique is leading his country into.
7.17pmOf Spain's nine nominees, six play in what would be described as defensive positions. After the retirements of David Villa and Fernando Torres, the country is looking for its new superstar attackers. Few would have put Rodrigo and Iago Aspas on a list of candidates for that role a few years ago...
7.19pmAspas has recovered from a nightmare spell at Liverpool to become one of La Liga's most prolific and consistent goalscorers. The 31-year-old bagged 22 in 33 matches for Celta Vigo last season.
7.21pmMeanwhile, Phil Brown did not think Rodrigo was good enough to displace Johan Elmander in his Bolton Wanderers side of eight years ago. The forward has since gone on to be a classy performer for Benfica and Valencia, transitioning from a winger into a central striker.
7.23pmCroatia themselves have five nominees for the FIFPro XI - the most they have ever received which should come as no surprise following their feel-good run to the World Cup final. Rakitic, Lovren, Sime Vrsaljko and the retired Mario Mandzukic join individual award nominee Modric on the shortlist.
7.27pmWith Rakitic and Modric in the centre of the park, Croatia have the type of world-class passers which England are crying out for. However, this lineup named by Dalic tonight does seem to be incredibly narrow and I am wondering from where they are going to find their width.
7.29pmThe introduction of the UEFA Nations League is designed to make friendlies more meaningful and place more emphasis on the result. Both managers have been speaking in that manner prior to kickoff. Dalic told UEFA.com: "It will be a tough match, so I think a draw would be good for us as well."
7.31pmDalic has also acknowledged that Croatia may find it more difficult following the World Cup as they are no longer going to be under-estimated. He told UEFA.com: "Croatia are the World Cup runners-up and all teams will be motivated against us – and we have to be aware of that."
7.33pmEnrique wants to see more of the same from his side, telling UEFA.com: "We will attack from the start. We'll try to have the ball, generate more chances than our opponents, press as high as possible. We need to dominate the important phases of play, that's our plan. We will be aggressive in that sense."
7.35pmSpain may be in for a more difficult test of their new methods tonight, with Croatia's technically gifted midfielders better equipped to deal with the intense pressing which flustered England. That midfield battle really is where it is going to be won and lost tonight.
7.37pmLess than 10 minutes until kickoff now at the Estadio Martinez Valero, which is the home of Elche CF who play in Spain's Segunda Division. It has a capacity of around 33,000 so a bit of a downsize from Wembley.
7.39pmSTAT: Spain have not suffered a competitive home defeat since 2003. Can Croatia end that run tonight?
7.41pmThe two teams are out for the national anthems. The goalkeeper Kalinic is a monster in the Croatia lineup. Modric cuts a diminuitive figure at the best of times but the 6ft 7in stopper really dwarves his skipper.
7.43pmPREDICTION: If Croatia play with the confidence which took them to Moscow in the summer they stand a chance but the lineup named by Dalic tonight does seem to be short on firepower. Spain have a little bit more magic about their attacking players and will nick this 1-0 or 2-0.
1 minKICKOFF: The action is underway - the three-time European champions against the World Cup runners-up. Should be a good one this. Croatia are in their changed black strip. Shame, their iconic home jersey is one of the great kits.
3 minSaul NIguez carries the ball skilfully through midfield but the attempted pass to the overlapping Gaya is cut out.
5 minCLOSE! Busquets' slack back-pass puts Spain in trouble and Croatia eventually tee up Rakitic to stroll onto a shot from 20 yards. De Gea is beaten but there is not quite the bend to bring the ball back inside the post.
7 minCarvajal makes an unchecked run to the right byline which Busquets finds with a lovely pass. The Madrid right-back knocks in a cross destined for Rodrigo but Mitrovic makes the clearance, albeit clumsily.
9 minWe spoke about Spain's high-pressing approach under Enrique but Croatia are outdoing them in that regard in the early going. Perisic is very busy indeed and it is causing errors in the Spain defence.
11 minAgain Carvajal has acres of space down the right but strays offside from Busquets' pass. That already looks as though it could be a profitable combination for the 2010 World champions tonight.
13 minCHANCE! Golden chance for Santini but he side-foots it wide from eight yards out. Vrsaljko makes the same sort of run that Carvajal has at the other end and picks out his man but the finish was lacking.
15 minCroatia's press really is relentless and well organised but Spain are continuing to take risks passing across the back.
16 minSAVE! Isco drops a cross over the back of the Croatia defence and Rodrigo flicks it goalwards with the outside of his foot. Kalinic reacts well to smother the ball but would have been disappointed to be beaten by an effort which did not generate much power.
18 minCHANCE! Carvajal has just made one of those defensive interventions that warrant the 'that's as good as a goal' treatment. Croatia work the ball wonderfully from Modric to Vrsaljko to Perisic who is just about to get his shot away from close range, but Carvajal had followed his run and made a crucial block.
20 minSUBSTITUTION: A big blow for Croatia as Vrsaljko is forced off with an injury. The right-back, now at Inter Millan, had been a great outlet in the early going so Dalic will hope that his replacement Marko Rog of Napoli can do the same sort of job.
24 minMidway through the first half and Spain take the lead with a wonderfully-constructed goal. Ramos spreads the play to Carvajal on the half volley, and the full-back lifts a cross into the box which Saul runs onto perfectly to thump a header past Kalinic. That is two goals in four days for the midfielder.
26 minPerisic gets to the left byline but spoons his attempted cross over De Gea's crossbar. Croatia should not be disheartened here as they started well and had a couple of chances to go in front themselves.
28 minIsco is penalised for a foul on club teammate Modric. There is competition for places in the Madrid midfield but new manager Julen Lopetegui may not be happy with that sort of challenge!
30 minKovacic gets the benefit of the doubt following a challenge on Gaya by the left touchline. Indeed the competition at Real is so strong that he's had to go to Chelsea of all places in search of game time!
32 minAfter a quiet opening half an hour we finally see something from Asensio who gets to the left byline and squares for Rodrigo, whose first touch is a little heavy and takes him away from goal.
33 minWe have certainly seen a little more of Asensio now because the Real Madrid prodigy has struck Spain into a 2-0 advantage. Croatia give the ball away midway inside their own half and Asensio picks up the ball and fires a 25-yard rocket past Kalinic before the visiting goalkeeper can move!
35 minAnd suddenly this is the Marco Asensio show! Spain quickly switch the ball to the 22-year-old who cuts inside the Croatian left-back and whips a shot past Kalinic off the underside of the crossbar. His first two international goals in the space of two minutes for Asensio- and both absolute raspers.
37 minThat second Asensio goal may actually go down as an own goal as it hit the back of Kalinic's head after coming down off the woodwork. That wouldn't take anything away from the quality of the strike though.
39 minYELLOW CARD! Brozovic enters the book for thudding into the back of Dani Ceballos on the edge of the Croatia box. He is the second player to be shown yellow this evening after his teammate Ivan Santini earlier in the half.
41 minSHOT! Asensio attempts to complete a memorable hat-trick with a free kick but, after showing outstanding technique and precision for his two goals, he fails to control a long-range shot which flies high.
43 minCroatia are passing the ball safely in midfield as if they are scared to lose it. That is most unlike the progressive Modric and Rakitic but it is the first they have seen of the ball in 20 minutes.
45 minRakitic wastes a good opportunity to deliver into the box as he overhits a free kick which De Gea claims comfortably.
45+2 minCLOSE! Spain very nearly get a fourth on the stroke of the break as Rodrigo directs a header just wide from Carvajal's cross.
8.38pmSpain strut off the field following the half-time whistle. They are in complete control in Elche and it is the new generation that has starred with Saul NIguez and Marco Asensio both on the scoresheet.
8.40pmWe've all heard of a game of two halves; how about a half of two halves? Croatia actually started the match as the better team but were shellshocked by three goals in 10 minutes and haven't recovered.
8.42pmThis is some reality check for Croatia who will be expected to compete with the giants of European football following their run in Russia. But they have been completely outgunned here by a Spain team who appear to have their swagger back after a couple of years in the international shadows.
8.44pmThings could have been very different had Croatia taken any one of their numerous early chances. Ivans Rakitic and Santini both struck off target from good positions in the opening 15 minutes, and Ivan Perisic was foiled by some tremendous last-ditch defending from the excellent Dani Carvajal.
8.46pmUPDATE: It is 0-0 between England and Switzerland after 45 minutes in Leicester. Gareth Southgate has rung the changes from the Spain defeat and the Three Lions have largely been second best.
8.46pmUPDATE: It is 0-0 between England and Switzerland after 45 minutes in the East Midlands. Gareth Southgate has rung the changes from the Spain defeat and the Three Lions have largely been second best.
8.48pmTwo brilliant, yet very different, strikes from Asensio. There is some magic in that left foot...
Marco Asensio's left foot is out of this world damn 😩😍🔥— OMAR 👑 (@Omaaar96) September 11, 2018
46 minKICKOFF: The action resumes at the Estadio Martinez Valero where both sides are unchanged for the second half. Croatia were forced into one early change remember when right-back Sime Vrsaljko went off injured.
48 minThe intensity with which Croatia started the first half has been drained out of them and they now seem to be in damage limitation mode having accepted defeat.
49 minDamage limitation mode isn't going so well for Croatia as Rodrigo makes it four for Spain early in the second period. The Valencia forward is on the shoulder of the last defender and times his run perfectly after incisive passing from Saul and Asensio, nutmegging Kalinic for his fourth international goal.
51 minThose four international goals for Rodrigo have come in just six starts. Perhaps Diego Costa has some serious competition on his hands?
53 minWas Lovren right all along? Is he really one of the best defenders in the world? Croatia have been so vulnerable in his absence. Domagoj Vida looks completely lost; not the same player from the World Cup at all.
55 minGaya has rapid pace and whizzes past makeshift right-back Rog to create space for a cross. It is into a delightful area and Rodrigo may have had a simple tap-in had Mitrovic not beat him to the punch.
57 minIt has been a new generation of stars who have shone for Spain tonight but there is still room for a Ramos goal. Some clever movement helps him shake off Vida and direct a header from a corner into the bottom corner, but it is way to easy for the prolific defender. This is getting embarrassing now for Croatia.
59 minSUBSTITUTION: Another one of the old guard - Busquets - makes way as Enrique gives us another look at the future with Rodri, the holding midfielder who joined Atletico Madrid this summer.
62 minSUBSTITUTION: I don't think many Croatia substitutes will be queuing up to come off the bench and into this feeding zone. Marko Pjaca is the unfortunate one to be plucked off the bench as Brozovic trudges off.
64 minSUBSTITUTION: Hometown hero Saul Niguez gets a standing ovation as he is replaced by Thiago, the Bayern Munich midfielder who did start against England and has won six domestic titles in a row. Not a bad sub.
66 minThis Croatia team appears to have been hit hard by a couple of high-profile retirements and absences. At 5-0, it is hard to argue that Lovren is not the biggest miss but they have struggled without Mandzukic too with Santini not providing the same presence or nuisance up top.
68 minFor the first time this evening this game has the air of a friendly about it. Spain have entered cruise control and Croatia - facing their heaviest ever international defeat - just want it to be over.
70 minSix for Spain; sensational Spain, again. Asensio is involved once more, making the most of the time afforded to him to roll the ball into the feet of Isco, who turns away from his marker and whips an unstoppable right-footed strike past Kalinic. It is another fantastic finish, made possible by the first touch.
72 minSUBSTITUTION: AEK Athens striker Marko Livaja is on for his second international cap as Santini gets out of the firing line.
74 minSUBSTITUTION: Carvajal has been magnificent tonight and gets a well-earned applause as he is swapped out for Azpilicueta. You have to be some player to keep the Chelsea player out and the Real Madrid right-back is definitely some player. Maybe the most complete right-back in the world.
76 minWhile Carvajal was outstanding there is no doubt that the star of the show has been Asensio. One goal and four assists - could this be the platform which takes the Real wonderkid to the next level?
78 minAsensio skips past Vida with a silky stepover and fizzes in a cross which MItrovic diverts away from danger.
80 minRamos overplays on the edge of his own box and invites Perisic to try to steal the ball from him. Cue a 50-50 between two absolute warriors who clash heads, with Ramos coming off worse.
82 minDani Ceballas won't take many headlines this evening but he has been so efficient with his use of the ball, and has been incessant with his pressing, charging down a clearance with eight minutes to go, with his team six goals to the good.
84 minSHOT! Rodrigo tries to bend a seventh into the far corner but his shot takes a deflection on its way behind for a corner.
86 minUPDATE: England have taken the lead against Switzerland through Marcus Rashford! That is now two goals in two games for the forward - can that kickstart his club season with Manchester United?
88 minCHANCE! Isco runs onto a pull-back 10 yards out and should score but hits his effort straight at Kalinic, who does not gather at the first attempt and is rescued from a possible seventh by Pivaravic's quick clearance.
90 minThere will be three minutes of stoppage time for Croatia to endure...
90+2 minThis result will send shockwaves around Europe. It makes you think how well England did to keep it to 2-1 the other day...
9.43pmSpain are back. They have sat in the international shadows for a few years but they have laid down a marker tonight with a 6-0 thrashing of Croatia who were World Cup finalists only two months ago. This Luis Enrique side is youthful, talented and exciting. Is this the start of a new Spain dynasty?
9.45pmThat's it from our coverage from the Estadio Martinez Valero. You can read our match report on a stunning Spain performance here. Thanks for joining us this evening and please ignore the score prediction at the bottom of this page! The Premier League is back this weekend. Until then, goodbye...