Strikeforce officials confirmed the bout to ESPN.com Saturday, adding it will likely headline the UFC 139 event.
Le (7-1), an accomplished kickboxer before switching to mixed martial arts in 2006, has fought his entire career under the Strikeforce banner.
Due to obligations in his acting career, the 39-year-old hasn't fought since June 2010. He avenged the only loss of his career in that fight, knocking out Scott Smith in the second round.
Le draws an equally explosive opponent in Belfort (20-9), who holds 14 career knockout victories. The latest came in his last appearance at UFC 133, where he dominated Yoshihiro Akiyama en route to a first-round finish.
The Brazilian is 6-1 since 2007, with the lone loss coming to middleweight champion Anderson Silva at UFC 126 in February.
A heavyweight title fight between champion Cain Velasquez and Junior Dos Santos had been originally scheduled to headline UFC 139 but has since been moved to a Nov. 12 card in Anaheim.
No official announcement has been made on what bout will take its place.
Brett Okamoto covers mixed martial arts for ESPN.com. Follow him on Twitter. ESPN's Chuck Mindenhall contributed to this report.