The 46-year-old Maresca succeeds Pep Guardiola and has signed a three-year contract.
"Manchester City is a club I know very well and having the chance to coach this team is a fantastic opportunity for me," Maresca said in a statement.
Enzo Maresca most recently came from Chelsea, where he was sacked in January after disagreements with management. He led Chelsea to victory in the Club World Cup and the Conference League.
Maresca has been at Manchester City before, first as an academy coach and later as an assistant to Guardiola.
He succeeds one of the most successful managers in history. Pep Guardiola led City to 17 titles in ten years at the club, including six Premier League titles and the club's first Champions League title.