Wade fired in 24 points while James provided 11 assists for the Heat, who trailed much of the first half but then put the game away with a 17-6 run the fourth quarter.
Minnesota, meanwhile, dropped its second straight in Florida after falling to Orlando Monday.
Andrei Kirilenko (22 points) and Nikola Pekovic (18, 12 rebounds) paced the Timberwolves.
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