Kevin Martin led the Wolves with 19 points.
Wade missed the last two games due to a knee injury and an illness, but he scored on the opening possession en route to a 19-point performance. Wade injured his right knee in the second quarter but immediately returned and played 32 minutes.
"Early on, you knew it was going to be tough, but I got a second wind and I felt pretty good," Wade said.
The Wolves struggled offensively and on the boards in their first game in six days and without Kevin Love. They shot a franchise-worst 29.3 percent from the floor without a starter shooting over 50 percent.
"We didn't move the ball the way we talked about moving the ball against them," Wolves coach Rick Adelman said. "You know what they are going to do. They are very active and long, jump, pick-and-rolls. The ball's got to move if you're going to get good shots."
"They're missing a big component; Kevin Love absolutely changes the dynamic of that team," Miami coach Erik Spoelstra said. "When he's not here, their game changes a little bit, and we were able to take advantage of that."
The Wolves had the largest first-quarter point differential in the NBA (108) entering Saturday's contest and held a 25-24 lead after the first period, led by Martin's 12-point quarter. But the Heat went on an 11-2 run with James on the bench to start the second quarter.
"To me it was just conscious effort," James said. "Always trying to go to the glass, always trying to go clean glass and get defensive rebounds, offensive rebounds and try to put more pressure on myself to help out."
Pekovic scored five points in the first two minutes of the second half as part of the Wolves' 11-4 run to trim the deficit down to 59-54, but the Heat quickly answered with their third-quarter run and the alley-oop marking the start of the blowout win.
NOTES: Heat guard Dwyane Wade returned to the court after missing Thursday's loss against the Bulls due to an illness. Wade said it has been frustrating missing five games this season. "You want to be out there every day, but it's a part of the game," Wade said. "Everyone deals with it in their way. Only thing I can focus on is when I'm able to get back on the court and try to go out there and help my team win." ... Wolves forward Luc Mbah a Moute made his first start with his new team, filling in for forward Kevin Love, who left the team due to the death of his grandmother. Mbah a Moute appeared in two games with the Wolves before this start. ... Heat forward Michael Beasley was a late scratch due to a hamstring injury. He is listed as day-to-day. ... Wolves coach Rick Adelman missed Friday's practice to be with his son, Wolves assistant coach David Adelman, and David's wife, Jenny, for the birth of their son, Leonard Joseph (LJ) Adelman. It's Adelman's eighth grandchild.