Overmars first joined a small Dutch club called SV Epe before joining Go Ahead Eagles. Willem II Tilburg later bought him from Go Ahead Eagles for ₤200 000 and during the 1991/1992 season, AFC Ajax Amsterdam bought him.

Marc Overmars became famous with Ajax under Louis van Gaal. He was a member of the Ajax team that won the European Cup in 1995 against A.C. Milan of Italy. However, soon after the final, he suffered a serious right knee injury in 1996, which kept him out of Euro 96. Despite his injury, Overmars was signed by Arsène Wenger's Arsenal in the summer of 1997 for ₤5.5 million. At the London club he scored vital goals, including one in the 1998 FA Cup final and another in a 1-0 victory over Manchester United at Old Trafford, which helped Arsenal to secure the Double. In the summer of 2000, he moved to Spain and joined FC Barcelona, for a record ₤25 million (€39.6 million), making Overmars the most expensive Dutch player of all time. This transfer was the first in the history of football to be announced via the player's personal website. Despite a difficult first season at his new club, Overmars was still an impressive performer, registering eight goals in 31 appearances. He was a regular feature of Barcelona's 2001-02 UEFA Champions League campaign in which he scored once in ten matches en route to the semi-finals, but failed to inspire FC Barcelona to any trophy success.

On February 24, 1993, he made his debut in the Dutch national team against Turkey. By the time of the 1994 World Cup, Overmars was a regular in the Dutch national team. In the 1998 World Cup, he was a regular fixture for Holland where he assisted his nation to a semi-final showdown with Brazil. Overmars was one of the best Dutch players in the tournament but suffered an injury in the 2nd round game against Yugoslavia (now Serbia). This ruled Overmars out of the next match, which was against Argentina. However, Overmars did enter late in the game as a substitute. He made an immediate impact by providing an inch perfect cross that almost led to a goal for the Netherlands. Overmars' injury became even worse after this game and he had to sit out the entire following match against Brazil. The Netherlands lost this match on penalties. Overmars was fit again to play in the Netherlands final match, which was the 3rd/4th play-off game against Croatia, but the Dutch lost 2-1.

In all, Overmars played 86 games for the Dutch national team, scoring 17 goals. Overmars was the youngest player to reach 50 caps with the Dutch national team. His final match was the Netherlands' loss to Portugal in the semifinals of the 2004 European Championships. By now, Overmars was being continually troubled by a persistent knee injury. After taking doctors' advice on the problem, on July 26, 2004, he announced his retirement from professional football. After his retirement he started working as a director for his first team, Deventer side Go Ahead Eagles.

He once said that he considers his former teammate Jari Litmanen as one of the greatest players ever. He is also best friends with Dennis Bergkamp