Mark van Bommel started his amateur career at local club RKVV Maasbracht before earning a professional contract with Fortuna Sittard in 1992. His other colleagues at Fortuna at that time who would later join PSV alongside him were Wilfred Bouma and Kevin Hofland.
Van Bommel was signed by PSV in 1999 where he formed a midfield partnership with Swiss international Johann Vogel. He won three Eredivisie titles and two Johan Cruijff Shield with the club. He was also named Dutch Player of the Year in 2001 and 2005.
In his final season with PSV, having assisted the team to the Dutch league title and a Champions League semi-final place, he was expected to join his father-in-law Bert van Marwijk who at the time managed the Bundesliga side Borussia Dortmund, but van Bommel opted to stay at PSV until the end of the 2004–05 season.