The Maple Leafs overcame a two-goal deficit in the third period, getting goals just 27 seconds apart from Lupul and Phil Kessel.
Kessel's game-tying goal 7:55 into the third period was his seventh of the season, giving him the NHL lead.
Lupul's second score of the game came with Zach Bogosian in the penalty box for interference. Moments after that goal was scored Winnipeg's Derek Meech was called for tripping and Kessel scored just 13 seconds into the penalty.
The first goal for Lupul came with 8:21 to go in the first period and rallied Toronto in a 1-1 tie. Winnipeg then took a 3-1 lead after two periods on goals by Alex Burmistrov and Mark Scheifele.
Winnipeg failed to build on its first win of the season, which came on Monday against Pittsburgh. The Jets had been trying for their initial road victory.
Toronto has won four of its first five games this season, its only loss having come in overtime.