Thomas Vermaelen began his football career at Germinal Ekeren in his native Belgium and he was in the youth team at the club before a merger changed the name of the club to Germinal Beerschot. Ajax Amsterdam signed Thomas Vermaelen from Germinal Beerschot in 2000 and he was in their youth team for over three years before his elevation to the first team during the second half of the 2003/04 season.
Vermaelen made his debut for Ajax Amsterdam first team during the 2-0 away win over FC Volendam on February 15, 2004. The centre back became a regular in the Ajax Amsterdam team upon his return from a loan spell as he was part of the squad that won the Dutch Cup in 2006 thus leading to a call-up to the Belgium senior national team. Thomas Vermaelen was part of the Ajax Amsterdam squad that won the 2006 Dutch Super Cup also known as the Johann Cryuff Shield and the Dutch Cup for a second successive season. Just like what was obtainable with the Dutch Cup, Vermaelen and Ajax Amsterdam won the Dutch Super Cup for the second successive season in 2007.
At Ajax Amsterdam, Thomas Vermaelen formed a potent central defensive partnership with fellow Ajax Academy graduate John Heitinga and then Jan Vertoghen when Heitinga left the club to join Spanish club Atletico Madrid. Vermaelen was made the Ajax Amsterdam skipper for the rest of the season when Dutch striker Klaas-Jan Huntelaar left the club midway into the 2008/09 season. Vermaelen was used as a left-back on a lot of occasions during the 2008/09 season.
Premier League heavyweights Arsenal paid an initial fee of €10m plus €2m in add-ons to sign Thomas Vermaelen from Ajax Amsterdam in the summer of 2009. He made his Arsenal debut during the 6-1 away win over Everton in the league.