Jerome signed for Birmingham City on 31 May 2006, for a transfer fee reported as an in itial £3 million, potentially rising to £4m. Sheffield United, West Bromwich Albion and Norwich City were also said to be interested. Jerome made his debut as a 66th-minute substitute against Colchester United on 5 August. However, it was a debut to forget, as he was sent off within five minutes of entering play elbowing an opponent in the face. He netted his first goal for Birmingham against Queens Park Rangers at Loftus Road on 12 September.
Jerome scored his first Premier League goal after 32 seconds of the away match against Derby County on 25 August 2007; his second goal of that game confirmed Birmingham's first win of the 2007–08 season. In July 2009, He signed a new five-year contract with the club. Jerome scored a spectacular first goal of the 2009–10 season to put his club into a 2–1 lead against Liverpool, described as "the kind of goal that only the likes of Gerrard usually score at Anfield"; he held off Javier Mascherano "before unleashing a 30-yard thunderbolt that flew beyond the reach of Reina and dipped under the crossbar".