The London derby had been billed as a chance for Berbatov to shine against his former club after such a wonderful start to his career in west London, but it was the man who so often lived in the Bulgarian's shadow at White Hart Lane who stole the show by bagging his 11th and 12th goals of the current campaign.
The England striker this week spoke about how working under Andre Villas-Boas had breathed life into his flagging career, and the 30-year-old delivered once again for his manager by killing off the game with Tottenham's final two goals after Sandro had opened the scoring with a 35-yard drive - his second goal for the club.
Berbatov looked determined to make an impression from the start and it took little time for him to turn on the class.
The Bulgarian, who enjoyed two prolific seasons at Spurs before leaving for Manchester United, produced a deft touch to skip past Michael Dawson and carve open the Spurs defence, but Hugo Lloris charged off his line to collect the ball before Steve Sidwell had a chance to shoot.
The away side then took the lead out of nowhere. Sandro capitalised picked up Mousa Dembele's pass five yards inside the Fulham half and carried the ball forward before unleashing a powerful drive that flew in off a post past Mark Schwarzer.
Fulham struggled to get back on the ball and Defoe took full advantage of Spurs' dominance. The striker broke down the middle to meet the pass of Gylfi Sigurdsson, who had turned Philippe Senderos inside out, and he made no mistake from close range.
Five minutes later and it was game over. Dempsey threaded a perfect through ball past Senderos, Defoe galloped through and slotted beyond Schwarzer.
Spurs took their foot off the accelerator and eased to a morale-boosting victory.