Wade, a 10-time All-Star, informed the Heat that he was opting out of the final two years on his contract, leaving him free to talk to any team when the free agent pool opens for business on July 1.
Media reports said Chris Bosh, the other member of the Heat's 'Big Three', had also terminated his contract but the Heat had not confirmed the move.
All three players had been widely expected to opt out of their existing deals to free up salary space for the Heat, then take less money in the short-term on fresh contacts with Miami which would deliver a much bigger pay day in the long-term.
Wade's decision came just three days after he, James and Bosh met in Miami to discuss their respective playing futures.
Power forward Udonis Haslem, a long-time friend of Wade's, also opted out of his contract with the Heat to become a free agent on Saturday.
"Today we were notified of Dwyane's intention to opt out of his contract and Udonis' intention to not opt into his contract, making both players free agents," Heat President Pat Riley said in a statement.
"Dwyane has been the cornerstone of our organization for over a decade, and we hope he remains a part of the Heat family for life.
"Udonis has been the heartbeat of this team for 11 years," Riley added. "He has sacrificed countless times to make this organization successful, and he is the epitome of what this organization stands for.
"We look forward to meeting with Dwyane and Udonis and their agent in the coming days to discuss our future together."
Wade has spent his entire 11-year NBA career in Miami after being taken as a first-round pick in the 2003 Draft, winning championship titles with the team in 2006, 2012 and 2013.
In partnership with James and Bosh, he has led the Heat team to four successive NBA Finals appearances over the past four seasons.
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