Lowry, who broke the franchise record for points in a preseason game set by Vince Carter (38), hit six 3-pointers and was 13 for 18 from the field.
"I've felt pretty comfortable every game. For me it's about maintaining, start off well, finish well," Lowry said. "It's only pre-season."
Cory Joseph added 14 points, Jonas Valanciunas had 13 points and Luis Scola 12.
Andrew Wiggins, the reigning NBA rookie of the year led the Wolves (0-3) with 21 points in 18 minutes. His older brother Nick, who was signed by Minnesota last month, scored four points in the final five minutes. He almost had six, but his final shot at the buzzer was waived off after originally being declared good.
The game was a homecoming, not just for Wiggins, who purchased 16 courtside seats for the game, but for Joseph and Anthony Bennett — both were playing their first games in Toronto for their hometown team.
"I was excited to play in front of my family, fans, friends," Joseph said. "Thanksgiving, so happy Thanksgiving to all the Canadians out there. We had our Thanksgiving the other night, they came out here to support me. A lot of love floating around here."
Bennett, whose defense has been impressive thus far, had five rebounds to go with three points in 19 minutes.
The Raptors and Wolves meet again in Ottawa on Wednesday as part of the NBA's Canada Series, which featured sold out games in Winnipeg and Vancouver, and then Ottawa and Montreal. The Raptors play the Washington Wizards in Montreal to cap the series on Oct. 23.