Toronto owned a seven-point lead midway through the fourth quarter, but the Bulls twice came back to tie the score.
DeRozan's foul shots gave the Raptors a 113-111 lead, after which Derrick Rose missed a jumper for the Bulls. Amir Johnson's layup put Toronto in front by four with 17 seconds remaining.
DeRozan had 24 points, as did Andrea Bargnani. Toronto shot an unusually high 58 percent from the field to win for just the 16th time, the third fewest victories in the Eastern Conference.
Rose scored 19 of his 32 points in the fourth quarter and had 10 assists. Carlos Boozer added 24 points for Chicago.
Joakim Noah returned to the Chicago lineup after missing 30 games with an injury to his right thump. He had seven points and 16 rebounds. Chicago had a four-game winning streak snapped.