Defoe netted five times when Tottenham thrashed Wigan 9-1 earlier in the season and scored a controversial opener on 27 minutes - finishing Gareth Bale's cross from an offside position.
On a terrible pitch Wigan failed to find any rhythm and after substitute Luka Modric struck a post, forgotten frontman Roman Pavlyuchenko wrapped up the points with a late double.
Spurs struggled to find their feet on the DW Stadium surface early on and Wigan almost took advantage when Hugo Rodallega caught the game's first sight of goal.
The 24-year-old Colombian exchanged passes with Marcelo Moreno before firing in right-foot shot that stung the arms of Tottenham goalkeeper Heurelho Gomes on 20 minutes.
But on 27 minutes the hosts were behind in controversial circumstances when Defoe fired home from an offside position.
Niko Kranjcar picked up the ball on halfway and slipped it wide to Bale on the left, the Welshman fizzed the ball across goal and Defoe - who was clearly offside - finished it off.
Following heavy snow and rain, the pitch - which Wigan share with Rugby League side Wigan Warriors - deteriorated throughout the contest.
But it was Spurs who adapted best and Defoe almost grabbed his second of the game when he combined with Kranjcar, only to fire straight at Chris Kirkland.
Wigan were struggling to gain a foothold in the game and Charles N'Zogbia failed to hit the target with a curling left-foot shot from outside the box six minutes later.
Peter Crouch should have put the game to bed in the 77th minute after collecting a pass from Tom Huddlestone, who was lucky to avoid a second yellow card for a late challenge on James McCarthy.
Substitute Modric struck a post at the death before Pavlyuchenko skipped clear to fire beyond Kirkland in the 84th minute, before repeating the trick in stoppage time to complete a comfortable win.