Since his debut in 1993, he has played over 50 times for the Colombian national team, making him alongside Mario Yepes the last active members of the original 1990s golden generation of Colombian football. He was named in the Colombian squads for the 1992 Olympics, two Copa América tournaments, two CONCACAF Gold Cups, and the World Cups of 1994, 1998 and 2014. On 24 June 2014, Mondragón made history by becoming the oldest player to play a FIFA World Cup match at the age of 43 years and 3 days, a record that was broken four years later by 45-year-old Egyptian goalkeeper Essam El-Hadary.