Klopas immigrated to the United States at a young age and received U.S. citizenship on his 18th birthday. In 1983, he signed with the Chicago Sting of the North American Soccer League straight out of high school, but an injury led to him missing out their final outdoor season. Klopas would play for the indoor Sting in the MISL for four seasons.
In 1988, Klopas returned to Greece to play with AEK and then moved to Apollon Athens in 1994. In 1996, he came back to the U.S. for the start of Major League Soccer, signing with the then-Kansas City Wizards. Klopas would spend two years with the club, and was then dealt to the expansion Chicago Fire. He would play two years for Chicago before retiring, helping them to the MLS Cup in 1998. In four years in MLS, Klopas scored 13 goals and added 16 assists.
Klopas made his debut for the U.S. national team in 1987 and scored 12 goals in 39 international appearances. He played for that country at the 1988 Olympics, was a member of the 1994 squad, and scored the game-winner in a 3-0 shocker over Argentina at the 1995 Copa America.
After retiring as a player, Klopas went into coaching, and spent time as head coach and general manager of MISL's Chicago Storm (2004-2006). In 2011 he was signed as manager for two years at Chicago Fire. From 2013 to 2015 he was manager at Montréal Impact.