The 32-year-old Los Angeles Galaxy forward has scored a record 138 goals in America's domestic league and won five MLS cups throughout his career.
On the international stage, Donovan is his country's leading goalscorer with 57 and his tally of 156 caps puts him second on the list of appearance-makers for the USA.
However, his time with the national team ended on something of a sour note when he was overlooked by Jurgen Klinsmann ahead of the recent World Cup.
Upon announcing his decision to retire, Donovan thanked those who had helped him throughout his distinguished career.
"After careful deliberation and after many conversations with those closest to me, I have decided that this will be my last season as a professional soccer player," Donovan posted on his official Facebook page.
"I don't write these words lightly and this day carries mixed emotions for me. I am sad to leave a profession that has brought me so much joy.
"However, after spending half my life as a professional soccer player, I also am excited to begin a new chapter and pursue other opportunities that will challenge me and allow me to grow as a person.
"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 feel incredibly blessed and lucky to have played a role in the remarkable growth of MLS and US Soccer during my playing career."
As well as the Galaxy, Donovan represented the San Jose Earthquakes and Bundesliga side Bayer Leverkusen.
He also joined Bayern Munich on loan in 2009 and enjoyed two temporary spells with Premier League side Everton, in 2010 and 2012.
LA Galaxy head coach and general manager Bruce Arena said: "Landon Donovan is one of the most significant figures in the history of soccer in the United States.
"His influence on MLS and soccer in this country will continue to be felt for many years to come."
