DeRozan grabbed 13 rebounds and made eight of nine shots from the foul line to help the Raptors improve to 25-13 at the Air Canada Centre.
Toronto’s win came courtesy of a fourth quarter scoring spree which saw them go on a 19-4 run that swung the game decisively in their favour.
It was the Celtics’ first defeat in five games and saw them fall to 23-15.
DeRozan’s masterclass was backed by a stalwart display from center Jonas Valanciunas, who finished with 23 rebounds and 18 points.
Toronto coach Dwane Casey paid tribute to Los Angeles-born DeRozan’s virtuoso display.
“He’s a tough kid, he didn’t grow up in Compton for nothing,” Casey said.
“He’s a tough kid. More than anything else, the 41 points is nice, but 13 rebounds, the 11 defensive rebounds when we needed it…
“DeMar came in and got some big rebounds, tough rebounds, so that was impressive. That was more of a sign of grit and grind as much as the 41 points.”