Raptors star Pascal Siakam led the way with a game-high 26 points on 9-of-16 shooting as the club secured its third straight division title and seventh overall.
Toronto's win also gave the club its fifth consecutive 50-win campaign.
It was the first meeting between the two clubs since last year's blockbuster deal that saw longtime Grizzlies star Marc Gasol traded to Toronto in exchange for Jonas Valanciunas, C.J. Miles, Delon Wright, and a 2020 second-round draft pick.
Gasol finished with 10 points and six boards against his former team while Valanciunas was held scoreless in 27 minutes of play.
It was another stingy defensive effort from the Raptors as the Grizzlies turned the ball over 22 times and were held to 40.7% shooting.