Vermaelen joined the AFC Ajax youth academy in 2000 and won the 2003–04 Eredivisie title in his first season with the club. He had a loan spell with RKC Waalwijk before rejoining Ajax and winning the KNVB Cup and Johan Cruijff Shield. After Klaas-Jan Huntelaar's departure in 2009, he served as club captain for the remainder of the season. He joined Arsenal in 2009 and was included in the PFA Premier League Team of the Year for that season. Following Robin van Persie's transfer to Manchester United in August 2012, he was named club captain.
Being left-footed, he usually plays as a left-sided centre back and can play at left-back as well. His key attributes include aerial ability, leadership skills, and his quickness with the ball at his feet. He is also known for his goalscoring ability as a defender.