La Roja will enter next summer's showpiece event in France having won the last two editions of the tournament.
Here, Sports Mole dissects the 90 minutes of action at the Estadio Municipal Las Gaunas.
On target: 9
On target: 1
Was the result fair?
With Spain only 1-0 ahead approaching the final 20 minutes of the contest, it could be argued that Luxembourg were unfortunate to lose by four goals, such is the effort that they put into the match. For long spells of the first half, the visitors frustrated Spain with a series of last-ditch challenges and excellent blocks. However, it was not much of a surprise when Cazorla sent La Roja into the lead in the 42nd minute. It was a similar story in the early stages of the second half, but it was always the type of game where Luxembourg needed to score the next goal if they were to stand a chance of securing a positive result.
That was not the case, however, with Alcacer racing onto a Cesc Fabregas pass to make it 2-0, before the Valencia forward scored his second of the night in the 80th minute. Five minutes later, insult was added to injury when Cazorla netted his second on what proved a comfortable night. Luxembourg deserve praise for what they put into the match, but just six shots - only one of which was on target - is an indication of their struggles. Spain, on the other hand, had 26 attempts and might have scored a couple more. A four-goal separation might be a touch harsh, but Spain certainly deserved to emerge victorious.
A number of injuries meant that head coach Vicente del Bosque could not select his strongest XI for this match and his problems worsened in the first period when David Silva and Alvaro Morata were both forced off injured. What should have been a comfortable first 45 minutes turned into a bit of a slog, with opportunities few and far between. Cazorla hit the crossbar in the first half, while Sergio Busquets and Jordi Alba also had good chances, but it took until the 42nd minute for the hosts to take the lead, with Cazorla having the simple task of scoring from close range after Pedro had been denied.
It took a bit of time for Spain to get going in the second half as Luxembourg continued to defend their lines, but there was not really a period of the match where Del Bosque's side threatened to lose control. At 1-0, Luxembourg were very much in the game despite their struggles, but Alcacer's fifth international goal effectively made sure of all the points. Alcacer, meanwhile, also made a strong case to be first choice in the final third as he scored his second in the 80th minute.
A final score of 3-0 would have been a fair reflection of the events, but Cazorla, who was impressive on the night, scored his second in the final five minutes. It was not exactly a performance that would have worried the likes of Germany and France ahead of Euro 2016, but Spain have now not conceded a single goal in a competitive match since last October. One look at the Spain bench here was an indication of their continued strength in depth and they simply cannot be written off ahead of the European Championships. It would take a brave man to bet against them making it three titles in a row.
On the face of it, a 4-0 defeat does not look great for Luxembourg, but head coach Luc Holtz can be proud of his team's performance. It was always going to be a massive ask for the Red Lions to make an impression against the European champions, but for long spells of the first half and sections of the second, they frustrated Spain. A five-man defence that included Kevin Malget, Maxime Chanot and Lars Gerson all impressed for the first hour, with the score still just 1-0 after 66 minutes.
The away side put so much into the first half, however, that the second was always going to be difficult. Neither team had a chance of note in the opening 20 minutes of the second period, but when Luxembourg's midfield switched off in the 67th minute, Fabregas set up Alcacer for 2-0. Visiting goalkeeper Jonathan Joubert will not look back too fondly on the third Spain goal, meanwhile, after a weak challenge on Alba led to Alcacer having the simple task of slotting home from 3-0.
It got worse late on when Cazorla added a fourth and in truth, Luxembourg were all over the place in the latter stages of the contest. For all of their work-rate and desire, they only had one shot on target and it did not trouble Iker Casillas. For Luxembourg, their wait to qualify for a major international tournament goes on, but they will be keen to avoid finishing bottom of the section as they prepare to host Slovakia, who need a positive result, in their final qualifier on Monday.
Sports Mole's man of the match
Santi Cazorla: The Arsenal midfielder has not always been an automatic starter for his country, but he made an important point here. It was the 30-year-old that opened and indeed completed the scoring against Luxembourg, but aside from his goals, it was the playmaker's touch and range of passing that impressed. He just about edged out fellow two-goal Alcacer for this accolade.
It is difficult to be too critical of Luxembourg, but as mentioned, their goalkeeper Joubert had a poor moment for Spain's third. The 36-year-old came out to challenge Alba inside the box, but it was a weak tackle from the stopper and Alba was allowed to find a cross into Alcacer, who could not miss. Jourbert should have been more decisive in that moment.
Referee Sebastien Delferiere can be pleased with his overall performance. The Belgian only issued four yellow cards and was always on hand to calm matters when tensions threatened to boil over. It was not exactly the most difficult game to officiate, but the 34-year-old contributed to what was an entertaining clash.
Spain: La Roja are now through to Euro 2016 as group winners, but face a Ukraine side on Monday that will be hoping to finish above Slovakia in second position.
Luxembourg: Luxembourg, meanwhile, host Slovakia as they attempt to secure second spot.