The Dutchman made seven changes to the Whites starting XI in a bid to end their run of five straight top-flight defeats, and his new-look side entered the break goalless with the top-four hopefuls.
Things got better for Fulham 10 minutes after the interval when Ashkan Dejagah scored his first goal for the club, firing low past Hugh Lloris after he was found unmarked on the right by Dimitar Berbatov.
However, Spurs turned the game on its head with two spectacular strikes, as firstly Vlad Chiriches and then Lewis Holtby scored from range to earn their side a first win in five Premier League matches.
Below, you can read how the London derby unfolded, courtesy of Sports Mole's live coverage.
7.07pmHello, all! Dimitar Berbatov's agent has told reporters that his client is looking for a move away from Fulham in January. But the big news is, he's in Rene Meulensteen's starting XI tonight!
7.09pmFulham's new manager has promised to get the best out of the Bulgarian, who has scored just twice this season. Can Berbatov find his scoring boots against one of his former clubs this evening?
7.11pmFull team news coming your way imminently, and there is also a notable selection in the Tottenham Hotspur forward line for this London derby, which comes to you from Craven Cottage.
7.20pmMeulensteen wastes little time in stamping his own authority on the Fulham team, making no fewer than SEVEN changes to the lineup that Martin Jol started with in the 3-0 defeat to West Ham United.
7.22pmBerbatov's return comes at the expense of another ex-Lillywhites striker Darren Bent, who is unavailable through injury, with Meulensteen opting to go with 4-2-3-1 in his absence.
7.24pmAshkan Dejagah and Alex Kacaniklic are both recalled, with Damien Duff and Adel Taarabt benched, and they, along with Pajtim Kasami, will be responsible for providing support to Berbatov.
7.26pmExperienced Greek international Giorgios Karagounis is restored alongside Scott Parker, playing against Spurs for the first time since leaving them in the summer, in front of the Fulham back four.
7.28pmSteve Sidwell, who made more Premier League appearances under Jol this season than any other Fulham player, is left out by Meulensteen, who names Philippe Senderos at centre-half.
7.30pmThe Swiss international partners Aaron Hughes, with Brede Hangeland still sidelined and Fernando Amorebieta omitted from the squad. There are also two changes for Fulham at full-back.
7.32pmSascha Riether has completed his three-match ban for stamping on Man United's Adnan Januzaj, while John Arne Riise is called back from his exile to make his first top-flight start since August.
7.34pmTottenham's changes are not quite as drastic, but Andre Villas-Boas does make three personnel alterations from the side that responded well to the 6-0 rout by Man City against United on Sunday.
7.36pmRoberto Soldado, who has just one open-play Premier League goal in 12 games this term, is only among the substitutes, with Jermain Defoe given the chance to impress as Tottenham's lone striker.
7.38pmIt is only the England international forward's second top-flight start of the season, and the same can be said of £30m summer signing Erik Lamela, who replaces Nacer Chadli on the Spurs left.
7.40pmThe Argentine was not in the Spurs squad for the visit of the Red Devils last weekend, but Villas-Boas may see this is an opportunity to give the 21-year-old, who has struggled to settle since arriving from Roma, more Premier League experience against supposedly weaker opposition.
7.43pmInjury appears to have robbed Moussa Dembele of the chance to face his former club. The Belgian is not in the Spurs squad, with Etienne Capoue, making his first top-flight start since the North London derby defeat to Arsenal on September 1, replacing him in their three-man midfield.
7.45pmHEAD TO HEAD: Spurs had won seven Premier League games in a row against the Cottagers until Berbatov scored the only goal in Fulham's 1-0 win at White Hart Lane in March.
7.48pmUPDATE: There are seven 7.45pm Premier League kickoffs tonight, and there has already been a goal in one of them. Nicklas Bendtner, making his first top-flight start for Arsenal since 2011, has given them the lead against Hull City inside two minutes at the Emirates Stadium.
7.50pmAround 10 minutes until kickoff now at Craven Cottage...
7.52pmMost people were unsurprised with Meulensteen's appointment considering that he was brought in as a coach under Jol while the Dutchman was under immense pressure, weeks prior to his firing.
7.54pmHowever, the former Manchester United coach has insisted that he did not come to the West London outfit to replace his compatriot, and that there are "no hard feelings" between the pair.
"People can think what they want, but it definitely was not the case that I came in to take over," the new boss told BBC Sport. "The reason I came was to work alongside Martin Jol. We were trying to take Fulham to the next step.
"I spoke to Martin Jol straight away [after he was sacked]. We had a long conversation, for maybe 30 minutes.
"There are no hard feelings between him and myself. We have known each other for more than 25 years."
7.57pmPREDICTION: Both teams are out of sorts at present, but you would expect Fulham to respond to the appointment of a new manager. Spurs are still struggling to find the net, so I think this one will be low scoring and that the hosts will begin their road to recovery with a 1-1 draw.
1 minTottenham get us underway, playing in their alternative light blue strip...
2 minInterestingly, Lennon looks to have started on the left flank, with Lamela operating from the right, where he is most comfortable. The pair were on opposite flanks in Spurs's hammering by Man City.
4 minFulham have had most of the ball in these very early stages, playing at a fast tempo which has what has been a deflated home crowd of late rocking. Riether slices a cross from the right behind.
5 minSAVE! Capoue intercepts a slack pass from Riise and releases Defoe first time. The forward runs at Senderos before shifting it onto his left foot and unleashing a low shot which Stekelenburg palms clear.
8 minThat Stekelenburg save could prove to be very important, as Fulham have only won one of their last 30 matches in which they have gone behind - their 4-1 victory over Crystal Palace in October.
10 minSpurs keep the ball on the halfway line for a while before Paulinho fails in a bid to find Defoe with a chipped ball over the top. That sums up Tottenham's season to date. Possession, but no penetration.
11 minKaragounis drifts in a lovely curling free kick from deep on the left, which Berbatov leaps to try and make contact with, but the delivery goes straight through into the safe hands of Hugo Lloris.
12 minCHANCE! Kacaniklic travels with the ball off the left, running across the Spurs defence before slipping in Berbatov, who would have been one-on-one with Lloris had his touch not been poor.
13 minBOOKING: Tough-tackling French midfielder Capoue, an £8m signing from Toulouse, picks up an early caution for a clumsy lunge on the lively Kacaniklic. Mark Clattenburg is tonight's referee.
15 minSAVE! Riise's fantastic flick inside takes two Spurs men out of the game and opens up some space for Karagounis to test Lloris with a stinging 25-yard shot which the keeper tipped around his post.
18 minUPDATE: Luis Suarez continues to haunt Norwich. The Uruguayan striker netted four against them last season and has already bagged a first-half hat-trick tonight. Liverpool lead 3-0 at Anfield.
20 minSandro charges in to win a 50-50 against Senderos and the ball falls to Defoe 20 yards out. He turns to run at goal, but his ex-teammate Parker was aware of the danger and pinched the ball from him.
23 minMISS! Spurs should be ahead following a brilliant counter attack from a Fulham corner. Dawson boots the set piece clear, and Riether's touch is heavy and allows Lennon to pounce. He releases Defoe through the middle, who in turn plays in Paulinho, who shows great composure to cut inside and beat two men before losing his cool to blaze way over the crossbar from 10 yards. This game is opening up...
25 minCHANCES! Before Paulinho's chance, Fulham twice came close themselves, with Berbatov forcing a great reflex save out of Lloris with a volley, and Vertonghen blocking a Dejagah header over the bar.
28 minMeulensteen will be delighted with the way his team have started. They have limited Spurs to little of the ball in the Fulham half, and created several chances which have forced good saves from Lloris.
30 minCLOSE! Spurs launch another quick break as Paulinho releases Defoe with a measured ball into the left channel. He holds the ball up before cutting it back to Lamela, who tries to cushion it first-time into the bottom corner, only to see his left-footed effort finish a yard or so wide. Decent effort.
32 minBOOKING: It is now a caution apiece as Kasami joins Capoue in the book for a high-foot challenge which caught the thigh of Dawson as the Spurs man was following through with his clearance.
34 minSAVE! Lovely play by Lamela, who has swapped flanks with Lennon in the last few minutes. He plays a one-two with Sandro before running into the space presented to him by the Fulham defence, and shooting, via a deflection, towards the top corner before Stekelenburg parried over the crossbar.
37 minCapoue wrong-foots Parker by rolling the ball smartly onto his left foot, but his 25-yard shot was always fading away from the top-right corner, which looked to be its intended destination.
39 minAt the other end, Kacaniklic is equally wayward with his effort. The Finn squares up Walker on the left edge of the box and creates room for a shot, which was still rising as it passed the crossbar.
42 minDejagah does brilliantly to wriggle his way into the box and then play a neat reverse pass to Kasami, whose cross towards Berbatov in the middle is blocked and then hoofed clear by Vertonghen.
43 minVery feint penalty shouts from Fulham, as Kacaniklic drills in a cross on the volley which strikes Sandro. The hosts think it hit him on the arm, but it definitely struck him high on the thigh.
45 minLamela pinches the ball from Berbatov and then holds off the challenge of the retreating Parker as he drives towards the edge of the box, from where he has a weak shot blocked by Senderos.
8.52pmThere are definitely signs of new-manger syndrome at Fulham where Rene Meulensteen's much-changed side have matched or even bettered Tottenham in most departments thus far tonight.
8.55pmKaragounis, Berbatov and Dejagah have all tested Lloris in the first half, but Spurs have had chances of their own, with Paulinho wasting the best of them, and Defoe and Lamela also coming close.
8.58pmIt is clear that Meulensteen's appointment has had some impact in the Cottagers dressing room. They are not playing like a team that has lost five Premier League matches in a row. Instead they are playing with confidence, especially those players buoyed by being recalled by their new head coach.
9.01pmBENCH WATCH: Spurs have an abundance of attacking options among their substitutes, with Soldado, Andros Townsend and Gylfi Sigurdsson, their leading Premier League scorer from open play this season, in reserve. Meulensteeen may turn to Tottenham flop Adel Taarabt for some extra creativity in midfield if things remain goalless until the later stages here.
46 minThe second period is underway at Craven Cottage, and I have news of a half-time Spurs change...
47 minSUBSTITUTION: Villas-Boas brings on Lewis Holtby for Capoue, who is short of Premier League game time and had been yellow carded. That change will see Paulinho drop into the midfield two.
48 minAfter Stekelenburg catches Holtby's deflected shot, he quickly releases Dejagah with a magnificent kick out of his hands, but Dawson comes across to muscle the Iranian off the ball.
50 minBLOCK! Holtby and Lennon combine well, with the winger getting on the end of the German's superb return pass. He squares for Defoe, who is thwarted by Senderos's brilliant stretching tackle.
53 minCHANCE! Lennon again looks for Defoe from the right, and although the pass is just behind him, the England frontman manufactures a chance with a back heel which is blocked. The rebound falls to Sandro, whose low 20-yard drive, bound for the bottom corner, is also foiled by a Fulham body.
56 minAshkan Dejagah opens his Fulham account and scores the first goal of the Meulensteen reign in the process! It's poor play from Dawson, who puts Paulinho under pressure with a dangerous pass, which Parker intercepts. Berbatov gets his head up and switches the play to Dejagah, who is in acres of space on the right. His first touch is great, and his second even better as he smashes it into the bottom corner.
60 minSUBSTITUTION: Karagounis, 36, has put in a great shift thus far but his work for the evening is over. Steve Sidwell is on in his place to offer Fulham some fresh legs in the middle of the park.
62 minThere is a coming together between Dawson and Senderos, who kicks the Spurs defender in the back a couple of times, while trying to get the ball, which had dropped out of Lloris's hands after Senderos had knocked Dawson into the Frenchman from a Fulham set piece. All handbags, really.
64 minKacaniklic passes inside to Sidwell, who shifts it on for Kasami, scorer of that wonderful volley against Palace, to completely miscue a bobbling shot which rolls into Lloris's gloves.
67 minSpurs don't seem to have many ideas going forward. A slow, unadventurous passing move eventually results in Lamela crossing hopefully into the middle, and Hughes heads clear.
69 minSUBSTITUTION: Another change from Villas-Boas, as Nacer Chadli comes on in place of Sandro, a switch which will likely see Holtby drop deeper. Spurs fans may be wondering why it isn't Soldado or Townsend, who was by far their best player earlier in the season, that have been introduced.
71 minSpurs fans shout for their players to move the ball forward as Defoe plays a pass into Holtby, whose return to the former Portsmouth striker was too forceful for him to control as he entered the box.
73 minOn a night of first goals, Chiriches has scored his first in a Spurs shirt, and my word it is spectacular! Walker's poor corner is cleared by Kacaniklic at the near post, and the ball drops for Chiriches to hit, with his weaker left-foot on the half volley, as clean as a whistle into the bottom corner. Stekelenburg is unmoved, and stunned, as are most of the other people inside Craven Cottage!
76 minCHANCE! Defoe exploits Senderos's lack of pace by running in behind to latch onto Walker's fantastic long ball. He chests it down perfectly, but then prods left footed over from 12 yards.
78 minSUBSTITUTION: Villas-Boas's final throw of the dice is to chuck on Townsend. Lamela, who had a bright first-half but a very quiet second, is the man sacrificed.
80 minSAVE! Lloris is at full stretch again to deny Berbatov, who had cleverly guided Kacaniklic's cross towards the bottom corner before Tottenham's keeper dived to palm it around his post and behind.
82 minSpurs have turned it around with another brilliant strike! Holtby drifts in from the right flank, knocks the ball past the tired legs of Parker and thumps a left-footed shot into the top corner.
84 minSAVE! Stekelenburg keeps Fulham in this tie with an absolute wondersave! Walker does really well to keep the ball in play on the right and then find Holtby, who delivers a cross to the near post for Paulinho to meet it with glancing header, which the Dutchman superbly tips over the crossbar!
86 minSUBSTITUTION: Meulensteen swaps Parker and Kacaniklic for Damien Duff and Bryan Ruiz as he looks to snatch an equaliser from this entertaining and action-packed London derby.
88 minSAVE! Ruiz nearly has an immediate impact, but he is denied by a Lloris save which eclipses Stekelenburg's at the other end minutes earlier. Fulham pump the ball into the box, and Berbatov holds off Dawson and chests it down for Ruiz to volley. His shot is deflected, and Lloris, who had already gone to ground, shows superb reflexes to get his other hand to the effort and tip it wide.
90 minWe are entering the first of THREE minutes of second-half stoppage time...
90+3 minWOODWORK! Fulham come within inches of snatching an equaliser as Kasami shoots through a crowded penalty area and against the post. When Lloris doesn't deny them, the woodwork does!
9.54pmA much-improved display from Fulham, who will take plenty of positives from Rene Meulensteen's first match in charge, where only two magnificent Spurs strikes denied them a share of the spoils.
9.57pmAshkan Dejagah gave Fulham a 56th-minute lead with his first goal for the club, but Vlad Chiriches and Lewis Holtby each opened up their Premier League accounts for Tottenham with spectacular left-foot efforts from range to snatch Andre Villas-Boas his first win in five top-flight matches.
10.00pmThat's it from me for this evening. Be sure to rejoin Sports Mole for our coverage of this weekend's Premier League fixture list. Villas-Boas can breathe a bit easier, for now...