Ikeme progressed through Wolverhampton Wanderers' academy and made the first team squad in their 2003–04 Premier League season. Due to Matt Murray's long term injury, he was promoted to the substitutes' bench for a string of games but never played.
To gain first team action, he moved on loan to League Two side Accrington Stanley. He made senior debut on 16 October 2004 when he played the first of four games for them, keeping a clean sheet at Aldershot Town. He also had a further loan move to Stockport County in Autumn 2005 which was cut short due to a hand injury.
He finally made his Wolves debut the following season, in a 5–1 win over Chester City in the League Cup on 23 August 2005. However, although often on the bench, he had to wait until 26 August 2006 for his first league appearance for the club when he appeared as a late substitute in a 1–0 win over Luton Town.
Ikeme suffered a knee injury during the 2006–07 season and had to undergo surgery, which kept him out of contention until late 2007. After recovering, he was an unused substitute or only employed in reserve team fixtures. It was not until September 2008 that he got his chance to return to Wolves' first team after regular keeper Wayne Hennessey was suspended. Impressing, 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 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 Robert Elliot, making five appearances. Upon the end of this loan he immediately went out on loan again, this time to Championship side Sheffield United for a month but a hamstring injury halted his stay. He recovered from this setback and was again sent out on loan to a Championship club, this time Queens Park Rangers during January 2010, where he made 17 appearances.
In August 2010, he again went out on loan when he joined Leicester City on a one-month emergency deal as cover for injured keeper Chris Weale. This spell was later extended but ended when the Foxes recruited Chris Kirkland at the end of November, after four appearances by Ikeme. He spent the remainder of the 2010–11 season back at Wolves.
Ikeme completed a one-month loan move to Championship side Middlesbrough in August 2011, after impressing in a pre-season trial. This loan deal was extended for a further month in August, and then for a third and final month until 1 November. He kept six clean sheets in ten games before a hand injury saw him return to Molineux.
Once recovered, he had a loan spell at another Championship side when he joined Doncaster Rovers in November 2011. He made five appearances for the club as they struggled at the foot of the table before the deal expired in January. He returned to them once again in March 2012, joining on an initial one-month loan deal, later extended to run until the end of the season. However, he was recalled by Wolves following an injury to first choice goalkeeper Wayne Hennessey; by this point, Doncaster had been confirmed as relegated to League One under his future Wolves manager Dean Saunders.
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 fifty-first minute of a 3–2 loss to Wigan Athletic at the DW Stadium on 13 May 2012. This was Terry Connor's last game in charge of Wolves before being replaced by Ståle Solbakken, who gave Ikeme his most consistent run in the first-team so far.
Ikeme started the 2012–13 season as Wolves' first choice goalkeeper in the Championship following injuries to Wayne Hennessey and Dorus de Vries; he maintained his place in the first team when the latter returned in September 2012. In March 2013 he conceded a bizarre own goal during a league game against Bristol City, when he allowed a David Davis backpass to go between his legs and roll over the line. Ikeme was substituted at half time, and it was later confirmed that he had broken his hand during the interval by punching a tactics board in the dressing room in frustration at the incident. This injury kept him out for the remainder of the season, which ended in relegation to League One.
Ikeme retained the goalkeeping position at Wolves for the 2013–14 season, excelling in a 3–0 win over Colchester United at the Colchester Community Stadium on 5 October 2013 when he saved a late penalty from Freddie Sears. However, he again suffered a broken hand when he was injured in a collision against Tranmere on 1 January 2014. He returned to Wolves' goal now as the established first choice, following the sale of Wayne Hennessey, and was a part of the team that won the League One title with a record points tally. After keeping 22 clean sheets across the season Ikeme was named in the PFA League One Team of the Year alongside four other teammates.
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.
During the 2016–17 season, Ikeme extended his current deal, ensuring he is contracted to Wolves until summer 2020. The goalkeeper received his first career red card on 21 January 2017 in a league match at Norwich City; when Wolves appealed against it, the suspension was reduced from three matches to two.
Ikeme was born in Sutton Coldfield, West Midlands, and was eligible to represent England or Nigeria at international level. He chose Nigeria, and was first called up to the Super Eagles squad in 2007. He made his international debut for Nigeria on 5 September 2015 against Tanzania in a 2017 Africa Cup of Nations qualification game.
On 6 July 2017, it was announced that Ikeme was diagnosed with acute leukaemia after returning abnormal blood tests during a routine pre-season check-up.As of 8 July 2017
Football League Championship: 2008–09
Football League One: 2013–14
Football League One PFA Team of the Year: 2013-14