The high-profile, 185-pound tilt will headline the event, which will air on Fox Sports. UFC officials confirmed the booking on Friday, after an initial report by Brazilian news source Globo.com.
A former UFC light heavyweight champion, Machida (20-4) made his middleweight debut last month in a first-round knockout victory over Mark Munoz. Following that performance, ESPN.com ranked Machida, 35, the No. 4 middleweight in the world.
Mousasi (34-3-2) elects to drop to middleweight despite being unbeaten in his last seven appearances at 205 pounds, including four finishes.
A former champion in Strikeforce, Mousasi made his UFC debut earlier this year, defeating late replacement Ilir Latifi by unanimous decision in April. He held the 205-pound Strikeforce title for eight months, after knocking out Renato Sobral in August 2009.