[4] In the 2006–07 season he was regularly called up to the first team and on 11 February 2007 he made his debut in Serie A at age 18, against Reggina (1–2), as a starter under coach Alberto Zaccheroni.

[8] On 11 July 2013, Ogbonna underwent a medical at Turin's Fornaca, Isokinetic and the Istituto di Medicina dello Sport ahead of his proposed cross-town move to Juventus.

[13] He was also a member of the side which won the 2013 Supercoppa Italiana[13] In the 2014–15 season, Juventus defended the Serie A title once again, with Ogbonna making 25 league appearances, and the 2014–15 Coppa Italia.

[13] On 10 July 2015, Ogbonna joined Premier League club West Ham United, on a four-year contract, for €11 million to be spread over the next three financial years.

[14][15] He made his debut 20 days later in the Europa League third qualifying round, starting against Astra Giurgiu; in the 82nd minute he netted an own goal equaliser as West Ham drew 2–2 at the Boleyn Ground.

[16] On 9 February 2016, Ogbonna scored his first goal for the club, netting an injury-time match-winning header in the 121st minute of a 2–1 home win over Liverpool, in the fourth round FA Cup replay.

[23][24] In June 2024, West Ham announced that Ogbonna would be leaving the club at the end of the 2023–24 season; he made 249 appearances for the Hammers, scoring 13 goals.

[34] In October 2020, after a two-year absence, Ogbonna was called into the Italian squad by manager, Roberto Mancini, for two games in the Nations League.

[35] A strong and powerful central defender, Ogbonna is primarily known for his outstanding physical attributes;[36][37] he is also a competent tackler, and possesses a good positional sense, as well as an ability to read the game.

[36][37] Ogbonna was born to Nigerian parents who emigrated to Italy from Nigeria in 1983, settling in the city of Cassino in the central part of the country, but managed to obtain Italian citizenship only after his 18th birthday.