The former Chelsea boss succeeds Pep Guardiola, who won 20 trophies during a glittering 10-year reign before stepping down at the end of last season.
The 46-year-old Italian has signed a three-year contract, ending weeks of speculation, but the departure from Chelsea has been messy, the London club receiving financial compensation and issuing a stinging statement.
"Manchester City is a club I know very well and to have the chance to manage this team is a brilliant opportunity for me," said Maresca.
"City is an incredibly well-run football club. Everything they do is innovative, planned and purposeful. For a manager, that is a dream situation. It provides the consistency I need to do my job effectively."
City are understood to have agreed a compensation package with Chelsea to secure Maresca's services amounting to $32.6 million.
Maresca had more than three years remaining on his contract when he left Stamford Bridge in January after a poor run of form and a breakdown in his relationship with the club's ownership.
He was immediately installed as favourite to succeed Guardiola when the Spaniard announced he was to leave in the final week of the 2025-26 campaign.
Indeed, there had already been speculation linking Maresca with a return to City, where he was previously assistant manager, for several months.
Chelsea's statement, released as City confirmed their new manager's arrival, said the club "felt let down" when he resigned "as we believed that his head and heart were focused on another club and another opportunity."
It has been reported that the compensation deal includes a personal contribution from Maresca himself.
Maresca served as Guardiola's assistant during City's treble-winning 2022-23 season. As a manager he led Leicester to promotion to the EPL in 2024 before guiding Chelsea to Conference League and Club World Cup glory the following year.
He faces a tough challenge in following the most successful manager in City's history, but his previous work under Guardiola and familiarity with the club made him their preferred candidate.
"Enzo is someone who has always sought out opportunities to challenge himself and succeed in his managerial career. He brings a personality, passion and intelligence completely aligned to our needs," said City chairman Khaldoon Al Mubarak.