Wade wasn't sure he'd play up until about an hour before tipoff after getting hurt a night earlier, but he logged 40 minutes and led an efficient offense that shot 55 percent from the field.
LeBron James added 19 points, while former Bobcats guard Eddie House scored 16 and hit three consecutive 3-pointers early in the fourth quarter when the Heat took control.
Gerald Wallace broke out of his scoring slump with 25 points and Stephen Jackson also scored 25 for the Bobcats, who ran out of steam late as they returned from a 4-2 road trip.
A night after scoring 51 points in an emotional win over Orlando, James got into early foul trouble and watched as Wade took control of Miami's offense with a versatile performance. He hit 8-of-20 shots and the Heat used their depth to continue their impressive streak of play.
Zydrunas Ilgauskas, who played just 4 minutes against the Magic, scored 13 points on 6-of-7 shooting in 18 minutes. Mike Miller added 13 points off the bench and Miami overwhelmed Charlotte with a variety of offensive options.
House, who spent time on the Bobcats' first team in 2004-05, hit three consecutive 3s in Miami's 9-3 run to start the fourth quarter to go ahead 92-80. The Bobcats got within six points, but never any closer as they fell to 0-3 against Miami.
The Bobcats shot 47 percent, but made just seven of 20 field goals in the fourth quarter after their impressive road trip left them in the eighth and final playoff position in the Eastern Conference. But as they begin a difficult stretch - the Bobcats host Dallas Saturday and Boston Monday - they couldn't keep up with the Heat after a strong start.
James, who had a rare game in which he fouled out in Charlotte three years ago, sat out the final 6 minutes of the first half with three fouls - the last two coming in a 12-second span.
It was part of a strange, yet entertaining first half that saw Wade have to be separated from Jackson after the Bobcats guard was called for a flagrant foul and referee Derrick Stafford hitting Heat coach Erik Spoelstra with a technical foul.
Wade also got into a brief tiff with Wallace in the second half, but Charlotte couldn't stop him from his triple-double despite not being 100 percent after a hard fall Thursday night.
Wade arrived on the early bus, spent extensive time warming up and getting treatment before declaring himself fit to go.
Charlotte failed to capitalize on what it felt was its biggest edge: Point guard. D.J. Augustin was held to four points on 1-of-6 shooting and had five of Charlotte's 16 turnovers.
Notes: Bobcats coach Paul Silas, James' first NBA coach in Cleveland, joked at shootaround that James was "pretty good" against Orlando and added he wouldn't be criticizing him anytime soon. "The difference is I didn't say what (Orlando GM) Otis Smith said. Let sleeping dogs lie," Silas said. ... James noted all nine of his 50-point games have come on the road. "I haven't figured out how to do that at home yet," he said. ... Heat C Erick Dampier, whom the Bobcats traded for this summer only to waive him to clear $13 million from the salary cap, acknowledged he turned down a $2.2 million deal by Charlotte. But he said he "just wanted to see what else was out there" in hopes of playing for a contender. ... Bobcats F Eduardo Najera (illness) didn't play.