Antony, 25, had been struggling to find his footing at Old Trafford and had reportedly turned down several offers throughout the summer to secure a move back to the Spanish club.
During his six-month stint at Real Betis, Antony regained his form, scoring nine goals and providing five assists in 26 games.
As part of the €25m deal, Manchester United has agreed to a 50% sell-on clause on any future profit Real Betis makes from selling Antony.
