Miami won its fourth in a row with Wade scoring 29 points and LeBron James adding 25 to go with seven rebounds and seven assists.
The Heat shot 55 percent from the field. Wade and James combined to go 21-of-34.
Detroit inched in front by nine early in the second quarter, but Miami stormed back to take a nine-point halftime lead and built a 16-point cushion heading into the final quarter.
Greg Monroe made 12-of-17 shots for the Pistons and scored 31 points along with 12 rebounds. Detroit, however, lost its second in a row and saw its road record slip to 4-16 -- second worst in the Eastern Conference.