Kyle Connor scored twice and had two assists, and Connor Hellebuyck made 23 saves for the Jets (25-10-1), who are 5-1-1 in their past seven and had lost the past six games against Toronto (0-5-1).
John Tavares scored twice, and Joseph Woll made 20 saves for the Maple Leafs (21-12-2), who have lost two in a row.
Connor gave the Jets a 1-0 lead at 16:04 of the first period on the power play. After Gabriel Vilardi deflected a point shot from Josh Morrissey at the top of the crease, Connor put in the rebound from the bottom of the right faceoff circle.
Connor made it 2-0 at 1:16 of the second period when he tapped in a pass from Scheifele on a 2-on-1.
Tavares cut it to 2-1 at 5:25 on the power play when he put in a cross-slot pass from Mitch Marner at the side of the net. It was his 200th goal with the Maple Leafs.
Scheifele pushed it to 3-1 at 3:27 of the third period when he beat Bobby McMann for positioning to the top of the crease and redirected a pass from Vilardi.
Scheifele jammed in a loose puck from behind the net for a 4-1 lead at 11:57 for his 20th goal of the season, the 10th straight season he has scored at least that many.
Tavares cut it to 4-2 at 13:42 when he took a pass from Jake McCabe and shot blocker side from the high slot.
Scheifele completed the hat trick with an empty-net goal at 19:39 for the 5-2 final.
Jets defenseman Haydn Fleury appeared to injure his right leg in a battle for a loose puck with Maple Leafs defenseman Connor Dewar and left the game at 19:06 of the second period.
The Maple Leafs were without defenseman Chris Tanev, who was scratched after taking the warmup because of a lower-body injury and captain Auston Matthews, who missed his second straight game with an upper-body injury.