DeRozan is the third player in Raptors history to score 50 or more in a game.
VanVleet also made a clutch free throw with nine seconds left in overtime - after missing the first of two attempts - to give Toronto some breathing room.
Giannis Antetokounmpo now leads the Eastern Conference with 16 games recording at least 20 points and 10 rebounds.
First meeting: Monday's game will be Toronto's first meeting with the Bucks since the two teams faced off in a first-round playoff series last April.
CHICAGO (AP) - Portland guard C.J. McCollum scored 25 of his 32 points after halftime, including the tiebreaking basket with 56.5 seconds remaining in overtime. His previous career high was 45 points against the Philadelphia 76ers last month on December 21.
Kris Dunn scored 22 points and reserve Nikola Mirotic had 18 points for Chicago, which blew a late lead for a second straight game.
Jimmy Butler starred for the triumphant Timberwolves.
DeRozan had little time for the typical aggressive trapping the Bucks did when he was running the offence, going off for 21 of his points in the first quarter. The team has won 11 in a row at the ACC, tying their second-longest streak at home. Los Angeles shot just 30.8 per cent from three-point range, and Jordan Clarkston led the team with 20 points off the bench. But it wasn't all about the scoring for the USC product, as he also led the Raptors in assists with eight to go along with five rebounds, one steal and one blocked shot.
It was pointed out to DeMar DeRozan that the Raptors are about to face a hard stretch of the National Basketball Association schedule with some excellent teams ahead, including a playoff rematch with the Milwaukee Bucks to open the calendar year. He hit two free throws 37 seconds later to reach the 50-point mark. Elfrid Payton added 17 points and Bismack Biyombo had 13 points and a season-high 17 boards.