The forward, who has spent part of his career with Bayer Leverkusen, Bayern Munich and Everton, has played more than 400 club games - most of them with San Jose Earthquakes and LA Galaxy - and won 156 senior caps for his country.
With five MLS Cups and three World Cup finals appearances to his name, the 32-year-old will wrap up what arguably is the greatest career in the history of American soccer after confirming that he will quit the game at the end of the campaign.
"After careful deliberation and many conversations with those closest to me, I have decided that this will be my last year as a professional soccer player," Donovan declared.
"It has been more than anything I could have dreamed of to represent the LA Galaxy, the San Jose Earthquakes, Everton, US Soccer and Major League Soccer throughout my career. There are so many people I want to thank who have inspired me, guided me and helped me on this incredible journey.
"I simply could not have accomplished what I did during my playing career without an overwhelming amount of support from my family, my friends and many others. I plan to express my gratitude to everyone in a more detailed manner at a later date; however, for now, I want to single out the fans. You are the lifeblood of this sport and, without you, none of us would be fortunate to call ourselves professional soccer players in MLS."
Donovan, the all-time top goalscorer for USA with 57 strikes, was surprisingly overlooked for this summer's World Cup finals by coach Jurgen Klinsmann.
In addition to his domestic titles, the attacker has won four Gold Cups at international level and was part of the USA side which finished runners-up at the Confederations Cup in 2009.