VanVleet made 17 of 23 shots from the field and 11 of 14 from 3-point range in the 123-108 win at Amway Center in Orlando, Fla. He also made all nine free throw attempts.
"I'm trying to enjoy it now, but it's not a championship or anything like that," VanVleet told reporters. "It was a good game for me. I'll enjoy all the love then get ready for the next one."
VanVleet caught fire early, scoring 17 points and five 3-pointers in the first quarter alone. He added another three shots from downtown and 11 points in the second to push the Raptors to a 64-60 halftime lead.
He poured in another 18 points in the third frame and scored eight points in the fourth to lead Toronto to its 15-point triumph.
Raptors forward Norman Powell also scored 23 points in the win and veteran guard Kyle Lowry chipped in 14 points, 10 assists, 10 rebounds and four steals.
Nikola Vucevic and Evan Fournier led Orlando with 21 points apiece in the loss.
VanVleet, 26, is now averaging a career-high 20.4 points per game this season. His 54 points on Tuesday topped the franchise-high of 52 points scored by former guard DeMar DeRozan in 2018. DeRozan was later traded to San Antonio for star Kawhi Leonard.
"Congrats to my brother Freddy V," DeRozan tweeted Tuesday night. "Kyle's old [butt] couldn't do it. Glad you did champ! Been telling you!"