It was a night of two special goals - the other coming from Vlad Chiriches, also his first in the Premier League and he became the first Romanian to score for the Club since Popescu in 1995.
Andre made a few changes to the side that drew with Manchester United at the weekend, with Etienne Capoue replacing the injured Mousa Dembele, Erik Lamela taking over from Nacer Chadli and Jermain Defoe coming in for Roberto Soldado.
Fulham, under new management, started with a bit of thrust, but the first opportunity fell to Defoe, who forced Maarten Stekelenburg into a good early save down to his right.
Scott Parker v Sandro was shaping up to be a no quarter given contest in the middle ground of Craven Cottage, but it was another ex-Spur, Dimitar Berbatov, who came close to making the next telling contribution when he flicked on a free-kick from Georgios Karagounis in front of goal. Thankfully, Hugo Lloris was not overly troubled.
Karagounis then scuttled forward and did force Lloris into meaningful action, with the goalkeeper making a good stop low down to his right.
Fulham came so close to taking the lead on 23 minutes when Berbatov spun in the area and cooly planted a shot towards the bottom corner and it took a brilliant save by Lloris to deny the Bulgarian. Then, at the other end, Defoe sprinted down the left channel and played in Paulinho. The Brazilian took on two players with ease to create a clear opening and then blazed over the bar.
The pace was pretty frenetic on a cold night on the Thames and Defoe showed a turn of pace dashing down the left just after the half hour mark and he proceeded to square for Lamela who went for placement and struck just wide. Moments later he unleashed a piledriver that was superbly saved by Stekelenburg.
There was a half-time change in the shape of Lewis Holtby being introduced for Capoue, with Paulinho dropping back into a more traditional midfield role and Holtby pushing up along with Lamela and Defoe.
Holtby was quickly into the action, swapping passes with Aaron Lennon to set the winger free down the right to deliver a cross that Defoe was just denied contact with by a good challenge from Philippe Senderos.
A Defoe backheel after good work by Lamela and Lennon almost caused alarm for Fulham inside the area, but a smashed shot from Sandro could have been more troubling with a brave block from Kasami.
Berbatov skimmed the side netting after a well-timed spin in the area to capitalise on a Sascha Rieter cross on 56 minutes, but Fulham didn't have to wait much longer to score and again Berbatov was involved.
He dispatched a defence splitting ball into the path of Ashkan Dejagah, who took it in his stride and drilled past an exposed Lloris.
A large part of the 24,128 crowd were lifted and found their voice as Fulham, buoyed by the goal, pushed on and sought to double the advantage.
On 68 minutes Sandro was replaced by Chadli, with Holtby dropping into midfield and the Belgian pushing up behind Defoe.
It was something of a relief on 72 minutes when a leveller came from perhaps an unlikely source. A corner directed towards the near post was cleared and landed in the path of Chiriches some 30 yards or so out. His shot was composed, low, true and well directed. So much so that it flew through everyone and into the bottom corner.
Defoe gave chase to a Walker clearance moments later and was not far away from securing a lead but could not keep his effort down.
Andros Townsend then took over from Lamela but Berbatov remained a threat and it took a fine save from Lloris to prevent him entering his name on the scoresheet with a cleverly directed flick.
On 81 minutes Holtby took charge after receiving the ball on the corner of the area, he then dribbled across and unleashed a piledriver that defeated Stekelenburg and flew high into the net. His celebration in front of the Spurs thousands was not reserved.
Lloris saved brilliantly from sub Bryan Ruiz in the 87th minute and there was one final scare in the last seconds of three minutes of added time when Dejagah fired towards goal, but Lloris was there to claw away.
Fulham (4-2-3-1): Stekelenburg; Riether, Senderos, Hughes, Riise; Karagounis (Sidwell, 61), Parker (Ruiz, 87); Dejagah, Kasami, Kacaniklic (Duff, 85); Berbatov. Subs not used: Stockdale, Taarabt, Zverotic, Boateng.
Spurs: Lloris; Walker, Chiriches, Dawson, Vertonghen; Capoue (Holtby, 46), Sandro (Chadli, 67); Lennon, Paulinho, Lamela (Townsend, 77); Defoe. Subs not used: Friedel, Naughton, Sigurdsson, Soldado.
Yellow cards: Fulham - Kasami, Senderos. Spurs - Capoue.
Goals: Fulham - Dejagah (56). Spurs - Chiriches (73), Holtby (82).
Referee: Mr M Clattenburg.