Wade experienced tightness in the hamstring during the first quarter of Wednesday's home loss against Indiana, but he played through the discomfort and led Miami with 20 points in 34 minutes.
Heat coach Erik Spoelstra initially told reporters after the team's Friday morning shootaround in Atlanta that Wade was questionable. After sitting out the session, Wade said it would be his first missed game of the season.
"Tonight, I'm not playing. It's as simple as that," Wade said. "It's just not smart for me to try and push it."
Wade is off to one of the most productive starts of his career as the Heat try to recover from the offseason departure of LeBron James, who returned to Cleveland in free agency after leading Miami to two titles and four straight Finals appearances.
The Heat entered Friday 5-3, with Wade having shaken previous injury issues to play in all eight games. That stretch included Wade playing in six games over a span of nine days, which included both ends of back-to-back sets on three occasions. Last season, Wade missed 28 games largely to address recurring knee soreness.
Wade is averaging 19.8 points, a team-best 6.4 assists and 3.5 rebounds a game. He suggested Friday the hamstring injury isn't a major concern at the moment and that he is sitting out as a precaution.
"I've had worse," Wade said. "I'll be back soon enough."
The Heat are in the midst of three games in four nights, with Friday's game followed by a back-to-back set against Milwaukee at home Sunday and a game Monday at Brooklyn.