Peter Crouch headed Spurs ahead, while Defoe scored from six yards after the break and then from a tight angle.
An unmarked Paul Scharner replied but Defoe notched from eight yards and Aaron Lennon scored with a low strike.
Defoe scored with two more crisp finishes, while Chris Kirkland scored an unfortunate own goal and Niko Kranjcar smashed home the ninth.
It is the first time a team has scored nine in a Premier League fixture since Manchester United thrashed Ipswich 9-0 at Old Trafford in 1995.
Defoe becomes only the third player to score five in one Premier League match after Alan Shearer and Andy Cole - and his exploits cannot have harmed his England prospects.
The first three of Defoe's goals came in a seven-minute burst shortly after the break - the second fastest hat-trick in the history of the Premier League. The quickest remains Robbie Fowler's for Liverpool against Arsenal in 1994.
And although Defoe was clinical in front of goal, Lennon was exceptional on the right flank - and he left the field to a deserved standing ovation when he was replaced by David Bentley after 79 minutes.
Tottenham, who move level on points with third-placed Arsenal after their biggest win in 32 years, led 1-0 at the break but the visiting Latics, playing in their awful orange away strip, were simply blown away in the second half.
Some of the Wigan defending was atrocious, with players gifting far too much time and space to the opposition in dangerous areas.
The Latics have now conceded 13 goals in their last two away fixtures - a real concern for boss Roberto Martinez. The result is Wigan's record league defeat - the previous being a 6-1 reverse against Bristol Rovers in 1990.
The visiting team were under the cosh from the opening minute, as Lennon burst into the box and sent a low ball across the six-yard box that Crouch stabbed wide.
Lennon, restored to the side after an ankle injury, ensured Wigan left-back Erik Edman, a former Tottenham player, endured a particularly torturous afternoon.
It was a cross from Lennon that Crouch converted for Tottenham's opener after nine minutes - although the striker should have already opened his account by then having also headed wide from a Wilson Palacios cross.
Kirkland saved from Palacios and Lennon, and deflected a Defoe strike on to his crossbar while Tom Huddlestone was inches wide.
For a while it seemed inevitable Tottenham would add to their lead but as the half wore on Wigan, previously overrun in midfield, began to assert a measure of control.
A low strike from Jason Scotland forced a sharp save from Heurelho Gomes, while an ambitious effort from out wide by Charles N'Zogbia glanced against the crossbar.
Even so, Spurs almost struck in first-half injury time when a jinking run from Defoe culminated with a strike that Kirkland, who despite the scoreline did make several world-class saves, tipped over.
Tottenham's pressure eventually told when a brilliant low cross whipped in from a deep position by Lennon was stabbed home by Defoe after 51 minutes. And from that moment on Wigan crumbled.
Three minutes later Defoe sealed victory with a smart low finish after some horrific Wigan defending failed to clear Palacios's optimistic pass from midfield.
Scharner gave Wigan the briefest of lifelines when he controlled a cross from the left before smashing the ball beyond Gomes.
The Austrian appeared to use his hand to control the ball but any anger Tottenham felt soon abated when they restored their three-goal advantage - Defoe tucking home yet another cross from Lennon.
It completed the second hat-trick of the season for Defoe after his triple in the 5-1 win at Hull.
Kirkland saved a Crouch header - a truly superb reaction stop -but could not stop Lennon scoring his deserved goal after Wigan stood off the winger to make it 5-1.Through balls from Corluka and Kranjcar were both converted by the rampant Defoe, the striker drilling the ball beyond Kirkland with each finish. Defoe has now scored 15 goals this season for Tottenham and England and is the top scorer in the Premier League.
Kirkland's misery was almost complete when a Bentley free-kick struck the woodwork and rebounded into the net off the Latics keeper.
There was just time for Kranjcar, allowed too much space in the Wigan area, to turn and smash the ball into the top corner deep in injury time.
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