He moved on a month-long loan to Conference Premier side Accrington Stanley on 14 October 2004, to fill the gap in their team caused by Jon Kennedy's broken leg.

[7] On 26 August 2006, he made his league debut for Wolves when he appeared as a late substitute in a 1–0 home win over Luton Town, replacing Murray for the final three minutes.

[9] He enjoyed his longest run of games in a Wolves shirt until injury ruled him out for the remainder of the season, during which the club went on to claim the Championship title and reach the Premier League.

After regaining fitness, he joined League One side Charlton Athletic on a month's loan in October 2009 to cover for injured Rob Elliot,[10] making five appearances.

Ikeme made his first appearance for Wolves since January 2009 on the final day of 2011–12, coming on as a substitute for Dorus de Vries in the 51st minute of a 3–2 loss to Wigan Athletic at the DW Stadium on 13 May 2012.

[20] Ikeme started the 2012–13 season as Wolves' first choice goalkeeper in the Championship following injuries to Hennessey and De Vries; he maintained his place in the first team when the latter returned in September 2012.

[26] Once back in the Championship, Ikeme impressed at the start of 2014–15, keeping five clean sheets in the first eight games, during which he saved an Owen Garvan penalty in a 1–0 win over Bolton Wanderers on 20 September 2014 at Molineux.

[30] On 6 July 2017, Wolverhampton Wanderers announced that Ikeme had been diagnosed with acute leukaemia after returning abnormal blood tests during a routine pre-season check-up.

[37] Ikeme made three appearances early on in Nigeria's successful qualification campaign for the 2018 FIFA World Cup, but could not go to the final tournament due to his cancer treatment, which manager Gernot Rohr called his greatest regret.

[38] Ikeme is a practitioner of Brazilian jiu-jitsu and has reached the rank of blue belt, along with winning the British Open and earning a bronze medal at the IBJJF European Championship.