Wade sliced through the 76ers' defense for 25 points and Jones tied a career high with five 3-pointers, including four in the final period. O'Neal added 19 points to go with 12 rebounds and six blocks.
The Heat's third consecutive win gave them the best record in the Eastern Conference at 8-3.
"This is like the best team I've been on in a while," O'Neal said. "We've got good shooters, and I've got people not worrying about their stats. It's a good fun team to be on, and I look to have fun this year."
"I thought everybody stepped up and played well in Allen's absence," said the 76ers' Corliss Williamson, who scored a season-high 18 points.
Wade had 17 points in the first half without missing a shot. He finished 7-of-13, capping his performance with an acrobatic reverse layup that brought a roar from the crowd, and shot 11-of-13 at the free-throw line. Jones matched a season high with 17 points.
O'Neal said his teammates failed to get the ball to him a couple times when he was open but shrugged off the oversights.
"They've never played with a big man of my caliber," he said. "I'm a special big man, you know."
The 76ers know it, which is why they sacrificed perimeter defense to contain O'Neal.
"You've got to give up something," coach Jim O'Brien said. "And they made shots."
O'Neal was a formidable presence on the defensive end, too, and the 76ers shot just 38 percent.
"He stepped it up defensively," Jones said. "We couldn't give him the ball as much as we wanted to. He just did it in other ways, getting rebounds and blocking shots."
The Heat increased their lead in the Southeast Division to one game over Orlando. They're 7-0 against the Eastern Conference but just 1-3 against the West.
"We're doing what we're supposed to be doing," O'Neal said. "We just have to keep getting better."
Marc Jackson scored 21 points for the 76ers, who lost their third consecutive game. Kyle Korver, making his first start this season in Iverson's absence, added 15 points.
Willie Green had 10 assists and zero turnovers but shot 1-for-14.
"We did some good things," O'Brien said. "We just didn't do enough to beat a good team."
The 76ers didn't lead until Korver hit a 3-pointer to put Philadelphia up 42-40. Miami trailed 58-56 midway through the third period before running off nine consecutive points -- including three free throws by O'Neal -- to grab the lead for good.
Jones' fourth 3-pointer gave Miami a 10-point lead for the first time at 83-73.
"All I can do is just try to continue to alleviate the pressure off of Dwyane and Shaq by making plays out on the perimeter," Jones said.
The Heat won despite 19 turnovers. The 76ers had 17.
Korver briefly left the game in the first quarter because of a gash in his forehead that required four stitches. ... The crowd included Chicago Cubs slugger Sammy Sosa. ... Each team was called for offensive basket interference twice. ... Stan Van Gundy earned his 50th victory with Miami, reaching the milestone faster than any other Heat coach, including Pat Riley. Van Gundy did it in 93 games, Riley 94.