"After a lot of thought, my family and I have decided that this is the right time for me to step away from the game," Dempsey said in a statement.
"I'd like to thank all of the team mates, coaches and support staff that I've worked with throughout my career. It has always been my dream to make it as a pro. I'm grateful to have been on this ride.
"I would like to thank all of the fans who have supported me throughout my career with the New England Revolution, Fulham, Tottenham, Seattle Sounders and the U.S. Men's National Team. Y'all have always made me feel at home, and it is something that I will always remember."
Dempsey is tied with former team mate Landon Donovan as the all-time leading goalscorer for the U.S. with 57 goals in 141 appearances.
Dempsey scored in three World Cups and captained the team at the 2014 tournament in Brazil where they reached the round of 16.
(Reporting by Hardik Vyas in Bengaluru, editing by Ed Osmond)
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