Born in Smygehamn, Isaksson began his senior career with Trelleborgs FF, where he played two seasons between 1998 and 1999.

After the 2006 FIFA World Cup, Isaksson completed a £2 million move to Manchester City of the Premier League on 15 August 2006.

He was expected to replace David James as their first choice goalkeeper, but due to knee and ankle injuries[6] and the form of Nicky Weaver, he did not achieve this.

Isaksson made his first appearance of the season for Manchester City by keeping a clean sheet in a 1–0 away win against Bolton Wanderers to put the team into the quarter-finals of the League Cup, on 31 October 2007.

he had a run of five league games in the first team, as part of a rotation used by manager Sven-Göran Eriksson to decide upon his first-choice goalkeeper.

On 9 July 2012, it was confirmed that Isaksson had left PSV after four seasons to join newly promoted Turkish side Kasımpaşa on a free transfer.

[13] On 11 August 2016, Isaksson signed a two-and-a-half-year contract with Djurgården, returning after 12 years away from Sweden and the club.

While at Djurgården, Isaksson established himself as the second-choice goalkeeper after Magnus Hedman for the Sweden national team, making his international debut against Switzerland in March 2002.

Isaksson was also the first-choice goalkeeper through Sweden's disappointing qualification campaign for the 2010 World Cup in South Africa as well as the qualifying rounds for Euro 2012 in Poland and Ukraine.

On 29 May 2012, national team manager Erik Hamrén announced his final 23-man squad for the Euros, including the vastly experienced Isaksson.

[20] On 12 October 2012, in a World Cup qualifier in Tórshavn, Isaksson earned his 100th international cap while Sweden defeated the Faroe Islands 2–1.