Toronto has run off eight victories in nine games, a stretch that has come after the Raptors managed just four wins in their first 23 outings.
After taking a 16-6 lead, Toronto opened a 16-point advantage at halftime and coasted during the final two periods.
DeRozan scored 24 points and Ed Davis had 19 for the Raptors, but they were the only starters who scored. With the game in hand, the bench players got plenty of time and combined to score 59 points. Terrence Ross had 26 points in a backup role and Amir Johnson added 17.
Portland, which had won its previous two contests, was led by 18 points from Damian Lillard.
Toronto shot 53 percent from the field and held Portland to 4-of-22 from 3-point range.