Antawn Jamison scored 22 points and Delonte West added 15 for Cleveland, which won its third straight. Anderson Varejao had 11 points and eight rebounds before fouling out with 2:12 left in the fourth quarter.
Jarrett Jack and Andrea Bargnani each scored 24 points for the Raptors, while Hedo Turkoglu had 18 before fouling out in overtime.
Reggie Evans scored a season-high 13 points, Sonny Weems had 11 and Antoine Wright added 10 as Toronto lost consecutive home games for the first time since Nov. 29 and Dec. 1.
The Cavaliers have won 15 of their past 18 meetings with the Raptors.
Varejao started in place of Shaquille O'Neal, who left Thursday's win at Boston with a sprained right thumb. O'Neal is scheduled to have an MRI Saturday.
Chris Bosh (left ankle) missed his fourth straight game for Toronto, with Rasho Nesterovic replacing him in the starting lineup. Toronto is 2-2 without Bosh.
Cleveland led 105-98 with 3:39 to go, but Bargnani hit a step-back jumper, Turkoglu made a reverse layup and Wright made a pair from the line to cut it to one at 105-104, with 2:12 remaining.
James ended the run with two free throws but Turkoglu tied it with a 3-pointer from the wing, then gave Toronto a 109-107 lead with a put-back dunk on Jack's missed layup with 50.6 seconds left.
James tied it with a layup, Jack made two free throws but James answered with another driving layup, making it 111-111 with 13 seconds remaining.
Toronto gave the ball to Turkoglu, but he missed a 3-pointer from the wing, giving Cleveland one second for a final shot. After a timeout, the Cavaliers gave the ball to Anthony Parker but he missed a 3 at the buzzer, sending the game to overtime.
Williams made 3-pointers on Cleveland's first two possessions in overtime and the Raptors never challenged again, shooting 1-for-8 in the extra session.
James stayed in the game after he went down wincing with an apparent left knee injury following a collision with Demar DeRozan in the first. He later threw down a driving dunk, forced a steal and made one free throw, then hit a 3-pointer after Cleveland grabbed the rebound on his missed second shot.
The spurt put the Cavaliers up 10, and they led by as many as 12 before Toronto rallied, cutting it to 33-30 after one quarter.
The Raptors kept it close through the second, and Antoine Wright's 3-pointer with 3.9 seconds left in the half tied it at 60 heading into the break.
West scored four points in the final minute of the third to give Cleveland an 86-82 lead heading into the fourth.
Notes
Cleveland recalled forward Darnell Jackson from the Erie BayHawks earlier Friday. … O'Neal ate dinner in the media lounge while watching Olympic speed skating on TV. … Actress Elisha Cuthbert and boyfriend Dion Phaneuf attended the game, as did Canadian sprinter Donovan Bailey.