On 3 August 2016, it was announced that Jesus would sign for Premier League club Manchester City in January 2017 on a contract until the summer of 2021.[23] City paid a reported fee of £27 million/€33 million, plus add-ons.[24] The transfer was fully completed on 19 January 2017.

Jesus made his first Premier League appearance on 21 January, coming on as an 82nd-minute substitute for Raheem Sterling in a 2–2 draw with Tottenham Hotspur at the City of Manchester Stadium.[25] A week later, Jesus made his first appearance in Manchester City's starting XI, assisting a goal for Sterling in a 3–0 FA Cup win over Crystal Palace.[26] On 1 February he made his first Premier League start in place of Sergio Agüero, and assisted Kevin De Bruyne in the 17th minute and then scored his first goal for the club in the 39th. With this, he became the first Manchester City player to have a goal and an assist in their first Premier League start, as well as only the third City player to be involved in two or more goals in their first Premier League start.[27] In his fourth game (third league start) Jesus broke a metatarsal in his right foot and was expected to be out for the remainder of the 2016–17 Premier League season.[28] However, he returned in April for the Manchester Derby, coming on as a substitute in a goalless draw.[29] Jesus ended the 2016–17 season with 7 goals and 4 assists in 11 games.[30]

He scored his first Premier League goal of the 2017–18 season on 26 August, an equaliser in a 2–1 away win over AFC Bournemouth,[31] and added two more in a 5–0 win against Liverpool on 9 September.[32] He had a 14-game goal drought between 18 November 2017 and 7 March 2018 that encompassed a knee medial ligament injury on New Year's Eve, and after breaking his duck in the Champions League loss to FC Basel he admitted that fear of getting injured was affecting his game.[33] Jesus scored the last Premier League goal in the 2017–18 season against Southampton in the 94th minute, to secure City a league record 100 points.