Playing in front of a raucous home crowd, the Raptors wasted no time getting their fans into the action with a 16-point lead after the first quarter.
Toronto never looked back in the second half, and Houston never got closer than five points down the stretch as the Raptors snapped a six-game Rockets winning streak.
Houston shot 1-for-9 from 3-point range in the first half. It was one of Houston's lowest-scoring quarters of the season.
On Friday, the Toronto Raptors showed exactly why they're at the top of the Eastern Conference standings.
Despite trailing by 15 at the half, the Rockets rallied in the fourth quarter behind another MVP-calibre performance by James Harden.
Houston entered the night averaging 15.5 3s made and 42.4 3s attempted per game, both figures significantly higher than the National Basketball Association records set by last season's Rockets.
Blake Griffin scored 25 points with eight rebounds and eight assists as Detroit snapped its four-game losing streak with a rout of Chicago in Detroit.
Trail Blazers 125, Warriors 108: CJ McCollum scored 30 points, Damian Lillard added 28 and Portland won its ninth straight game with a victory over short-handed Golden State in Portland. Lowry was 7-of-9 from beyond the arc.
DeMar DeRozan scored 42 points, then fed Fred VanVleet for the tiebreaking jumper from the left corner with 1.1 seconds remaining in overtime to lift the Toronto Raptors to a 121-119 victory over the Detroit Pistons on Wednesday night. DeRozan drilled a baseline turnaround over James Harden, his former AAU teammate, immediately after a Harden 3-pointer tied the score with a little more than two minutes remaining. It wasn't the 28-year-old's most efficient game of the season (8-19, 3-7 from three), but DeRozan came up clutch once again, responding to Harden's game-tying 3-pointer with a fall-away baseline jumper over Harden to restore Toronto's lead. They play under Mike D'Antoni, who values 3-pointers and layups more than any other shot in basketball.
Harden, who DeRozan declared this season's MVP earlier in the day, finished with 40 points on 15-of-22 shooting and gave Houston a chance to steal the game.
Lowry came out hot, exploding for 13 points in the opening quarter - including a trio of three-pointers as his Raptors shot 62 per cent from the field and compiled a shocking 32-16 first-quarter lead over the Rockets.
The Raptors became the first National Basketball Association team to clinch a playoff berth this season.
But Toronto's shooting quietly slipped to 45 per cent in the second quarter, while Houston improved to 55 per cent behind a nine-point quarter from Harden. Harden blasted off 14 third-quarter points on dunks, driving layups and three-point shots as the Rockets whittled away at that big Raptor lead.