Van Damme started his career at Beveren, before he made a short move to neighbour club Lokeren where he played in the youth teams. He then signed for Germinal Beerschot in 2001, making his senior debut in the Jupiler League. Beerschot were linked with Ajax and the Amsterdam club soon offered him a trial stay beginning in February 2002. In summer 2002, Van Damme moved permanently to Ajax where he showed promise in the Dutch Cup. In the 2002–03 season, he played in the Champions League and started as a regular player in the squad before breaking his toe in November 2002. The next season, he helped Ajax again qualify for the Champions League group stage but he had few chances to play in the first team's title winning campaign, with the club preferring the Brazilian Maxwell at full back. This limited chance of game time led him to sign for Southampton of the Premier League in June 2004, for £2.5 million. He made little impact during his spell with Southampton, playing just six times during the 2004–05 season, as the club were relegated to the Championship. He spent the 2005–06 seasonon loan at German Bundesliga club Werder Bremen but again struggled to hold down regular football, making just eight appearances, as the club finished runners-up. In search of more playing opportunities, Van Damme returned to his homeland to sign for Anderlecht in June 2006 for €500,000.
Anderlecht
His four-year spell at Anderlecht was much more successful as he won two Jupiler League championships and the 2008 Belgian Cup, and appeared in the Champions League group stages several times. Van Damme scored in the 2–1 win at rivals Club Brugge that won the second of these league titles in 2010. His time in Brussels was the source of an unsavoury incident however, when Standard Liege defender Oguchi Onyewu accused him of racial abuse alleging that Van Damme called Onyewu a "dirty monkey" during the 2008–09 Championship playoff between the clubs. Onyewu subsequently sued Van Damme, although the case was withdrawn in February 2011 after a meeting between the two players when Van Damme apologised for any offence he may have given.
Van Damme returned to the Premier League in June 2010 by joining Wolverhampton Wanderers. He signed a three-year deal, with the option of a fourth year, for a fee reported to be around £2.5 million. Sell-on clauses relating to his 2006 move to Anderlecht mean that Southampton should receive between 10 and 15 per cent of the fee received from Wolves, estimated at £300,000. He scored his first, and only, goal for Wolves against Fulham on 11 September 2010. He struggled to settle at the club though, and on 29 November 2010, he signed a pre-contract agreement to return to his Belgian homeland in a three-and-a-half year deal with Standard Liège, after just six appearances for the Midlands club.
Standard Liège
Van Damme's return to Belgium was officially ratified when the January 2011 transfer window opened. He made his Standard debut in a 0–2 loss at former club Anderlecht on 23 January.
In August 2017, Van Damme returned yet again to Belgium as he was signed by Royal Antwerp for $235,000. Van Damme said the main reason for leaving the LA Galaxy was that he wanted to be closer to his children.
Lokeren
On 3 July 2019, he signed a one-year contract with Lokeren.
Van Damme was married to former tennis player Elke Clijsters, sister of Kim Clijsters, from 2008 to 2016, whom he wed in May 2008 in Bree, Belgium. They have two children.
