The result of the match had been determined by half-time after Fulham had raced into a four-goal advantage by the break.
Danny Murphy scored from the spot 11 minutes in after Alan Hutton barged down Clint Dempsey in the box.
The Cottagers captain, who signed a new deal with the club on Friday, added a second penalty three minutes later after Michael Dawson was sent off for tugging back Moussa Dembele in the box.
Brede Hangeland stabbed home to make it 3-0 before Dembele rifled home a blistering strike just before half-time to seal the impressive win.
The win will provide another morale boost for Mark Hughes' resurgent side but will raise serious questions about Tottenham's ability to challenge for honours, particularly given that Harry Redknapp fielded arguably his strongest team available.
Gareth Bale was out due to a back injury but Redknapp named an XI that included the likes of Rafael van der Vaart, Steven Pienaar and Heurelho Gomes, who returned in goal after a shoulder injury kept him out of last week's draw at Newcastle.
Fulham, who had lost twice to Spurs already this year, replaced Chris Baird with Carlos Salcido in the only change from the XI that lost to Liverpool in midweek.
After a dull opening 10 minutes, the game sparked into life when Salcido robbed the careless Dawson 30 yards out before Hutton barged over Dempsey in the box as he raced towards goal.
Referee Phil Dowd blew for a penalty and Murphy fired the spot-kick to Gomes' right to put Fulham 1-0 up.
Dawson's match went from bad to worse two minutes later when he dithered on the ball just inside his own area. Dembele pinched the ball off Dawson before the England centre-half tried to yank the striker back by his shirt.
Dowd dismissed the former Nottingham Forest man before Murphy beat Gomes, this time to the goalkeeper's left, from 12 yards.
Buoyed by their excellent start, Fulham looked for a third goal and it came after 23 minutes.
Andrew Johnson flicked on Damien Duff's corner and the ball found Hangeland at the back post. With Gomes stranded, the Norwegian made no mistake from three yards.
Sensing Tottenham could crumble, Redknapp sent on William Gallas for Sandro but Spurs still looked weak at the back.
Luka Modric fizzed a shot wide from long distance and Van der Vaart went into the book after clattering into Murphy from behind just before the half-hour mark.
Fulham made their numerical advantage count by dominating play. Johnson raced at the Tottenham defence as the first half came to a close but his shot fell straight into Gomes' hands.
Dembele then rounded off an incredible first half for the hosts with a fourth goal when he strode past Sebastien Bassong and fired a sublime 20-yard strike past Gomes.
Redknapp brought on Peter Crouch for Defoe at the break as Spurs looked to get back into the game.
Crouch's introduction had little effect though as Fulham started the second period the stronger of the two sides.
Johnson flicked a header just wide of Gomes' goal from a John Pantsil cross.
At the other end David Stockdale had his first test of the half, saving a tame Sebastien Bassong header from Aaron Lennon's cross.
Dempsey's 25-yard curling shot caused Gomes to pull off an impressive save low down to his right just after the hour mark.
Dembele then skipped past two markers before Bassong blocked the striker's goal-bound effort from eight yards.
A fifth Fulham goal looked inevitable as they laid siege to the Spurs goal.
Dempsey raced at the Tottenham back four and beat Gomes from 25 yards but his rising strike flew over the Tottenham goal.
Redknapp brought the ineffective Van der Vaart off, bringing on Jermaine Jenas, and Mark Hughes took Johnson off and introduced Zoltan Gera.
Pienaar was lucky not to be booked when he hacked down Duff after 71 minutes.
Murphy received a standing ovation when he departed two minutes later to be replaced by Jonathan Greening.
The home crowd taunted their north London rivals as they struggled to get hold of the ball.
The match's tempo had dropped to that of a practice match by the time Simon Davies replaced Dembele with 10 minutes left.
A rare move down the Tottenham right allowed Hutton to cross for Crouch but the England striker was muscled off the ball by Pantsil.
Fulham almost had a fifth in the 87th minute when Aaron Hughes' glanced header hit the bar from Duff's corner.
Gera had a golden chance a minute later but Gomes saved with his feet from the Hungarian's 12-yard shot and Fulham had to settle for four.