Aaron Lennon may have turned in a star performance for the home side, but it was Defoe who stole all the headlines with five goals, showing Fabio Capello why he must be selected in the England squad for the World Cup finals next summer.
It took just seven minutes for Defoe to get his three goals - only Robbie Fowler has done better when he set the record for Liverpool back in 1994 against Arsenal.
Tottenham have not finished in the top four since 1990, but after producing one of their best ever performances in the Premier League, Harry Redknapp can start dreaming of seeing his side compete against the big teams in Europe once again.
Lennon wasted no time making an immediate impact on his return to the side when he played a crucial role in the opening goal on eight minutes.
The winger found space down the right hand side and his cross caused all kinds of problems for Titus Bramble who produced a shocking piece of defending in his attempts to clear the ball.
Peter Crouch found himself completely unmarked inside the box and he made no mistake heading home from close range.
The woodwork prevented Defoe grabbing a second for Tottenham on 33 minutes when he burst clear into the box and saw his powerful shot superbly tipped onto the bar by Chris Kirkland.
Defoe doubled Tottenham's lead on 51 minutes. Lennon was involved in the heart of the action once again when his cross picked out the England forward who got in front of Bramble and smashed the ball into the roof of the net.
The Tottenham striker added his second of the game on 54 minutes when he skipped past Emmerson Boyce and made no mistake firing a low shot past Kirkland into the corner of the net.
Wigan pulled back a controversial goal on 57 minutes when Hugo Rodallega's cross picked out Paul Scharner who clearly handled the ball inside the box, but the linesman somehow allowed play to continue as the Austrian midfielder hit the ball into the back of the net.
Tottenham put the game beyond Wigan when Defoe completed his hat-trick on 58 minutes. It was no surprise that Lennon was the provider once again as his cross fell perfectly for Defoe, who fired a volley into the corner of the net.
Lennon got his just rewards when he capped a man-of-the-match display with Tottenham's fifth goal on 64 minutes when his low shot flew past Kirkland.
The madness continued at the Lane when Defoe grabbed another goal on 69 minutes and it was to get even better for the home side when Defoe added his fifth of the game on 87 minutes.
Substitute David Bentley made it eight on 88 minutes with a curling free-kick from the edge of the box, with the aid of a touch from Kirkland, before Niko Kranjcar completed the rout in stoppage time.