After a first periodwith chances few and far between, the Bulgarian finally opened the scoring just after the interval following a swift counterattack from the away side.
Spurs failed to properly respond to the blow, with the best opportunities by some distance falling to substitute Jermain Defoe, who could not capitalise on either as Mark Schwarzer produced a couple of excellent saves to deny the Englishman.
As expected, Andre Villas-Boas made several changes from the side who almost capitulated against Inter on Thursday with Hugo Lloris, Steven Caulker, Michael Dawson, Benoit Assou-Ekotto and Gareth Bale coming in for Brad Friedel, Kyle Walker, William Gallas, Jake Livermore and Defoe.
Martin Jol, meanwhile, named an unchanged XI after his men secured a hard-fought 2-2 draw away to Sunderland on March 2.
Tottenham began the game very much in the ascendancy, with Sascha Riether having to clear an early Bale header off the line after just six minutes, following a dangerous Gylfi Sigurdsson corner.
That was the best chance in what swiftly became a turgid first half as, with both sides struggling to assert themselves on the game, perhaps the most significant incident came from an injury picked up by the talismanic Bale as the Welshman hobbled off gingerly following an ankle complaint just before the interval.
The winger returned after the break but it was Fulham who finally sprung the game into life with a goal, courtesy of a swift counterattack finished coolly by Berbatov. Ashkan Dejagah set Riether away down the right, with Spurs short at the back having been caught pushing for the opener, before the right-back set up the Bulgarian with a smart cross. The ex-Tottenham star duly tucked the finish home to open the scoring, refusing to celebrate against his former employers.
The visitors were inches away from extending their lead just five minutes later as, after a flick-on from a Giorgios Karagounis corner, Brede Hangeland headed just wide of the far post with Spurs struggling to find a response to Fulham's opener.
With 20 minutes remaining, substitute Defoe finally tested Schwarzer in the Fulham goal, though the Australian proved more than equal to his stinging effort from the edge of the box, palming away adeptly.
Schwarzer was to thwart the striker once more in the last chance of the game, producing an absolutely magnificent save to deny the Spurs frontman after Bale put the ball on a plate for Defoe in the six-yard box and, in doing so, retaining his clean sheet and securing a win for the away side.