Defoe stunned the hapless visitors and equalled the league's single match scoring record with a mesmerising second-half blitz at White Hart Lane after Spurs had gone in 1-0 up at the break thanks to a ninth-minute Peter Crouch header.
After hitting the bar in the 34th minute, Defoe opened his account in the 51st and completed his quickfire hat-trick seven minutes later - the fastest since Robbie Fowler's three in four minutes for Liverpool against Arsenal in 1994.
He netted again in the 69th and added a fifth with a right-foot shot three minutes from time as Tottenham fans sang "we want 10."
Aaron Lennon also struck in the 64th while shell-shocked Wigan keeper Chris Kirkland added to the goal tally in the 88th when a David Bentley shot rebounded off the angle, hit him on the back and went in.
Croatia's Niko Kranjcar scored in the dying seconds to wrap up Tottenham's biggest win for 32 years, when they beat Bristol Rovers 9-0 in the second division, and their biggest in the Premier League.
"The lads can't believe it," said Defoe. "If you look at the finishing, all the goals were unbelievable. I looked over at the manager and he looked shocked as well.
"It's like a dream, it's brilliant."
CONTROVERSIAL GOAL
Wigan's only reply was a controversial Paul Scharner goal in the 57th minute, with the player appearing to control the ball with his hand before scoring.
"The result is not normal. It's one of those freak games," said Wigan manager Roberto Martinez. "It was too easy for them to score their first three goals.
"I'm not bothered about the final scoreline. I'm more bothered about how naive we were in one-on-one situations.
"Of course it was a very good day for Tottenham. Their finishing was very clinical and every time they had a shot on goal they scored. But we were very, very naive for the first three goals."
NEWS: Redknapp revels in nine goal romp at right end
Tottenham are level on 25 points with North London rivals Arsenal but behind the Gunners on goal difference.
The top teams played on Saturday, with Chelsea (33 points) beating Wolverhampton Wanderers 4-0 to stay five clear of champions Manchester United who overcame Everton 3-0 at Old Trafford. Arsenal lost 1-0 at Sunderland.
Blackburn Rovers shrugged off the absence of manager Sam Allardyce, who is awaiting heart surgery, to beat his former club Bolton Wanderers 2-0 in Sunday's lunchtime kick-off.
Stoke City kept Portsmouth rooted to the bottom of the table with a 1-0 home win that sent them up to ninth.
Victory in the Lancashire derby ended Blackburn's run of 10 successive away defeats, the team's first points on their travels this season lifting them to 11th place.
Defeat left Wanderers third from bottom.
David Dunn netted
