Wambach, a native of Rochester, New York, who has been a key member of the U.S. women's football team, announced her decision shortly after the squad was honoured at the White House by President Barack Obama for winning the World Cup in July.
She scored 184 goals in 252 matches during a 15-year career in international play.
Wambach said she will retire after the U.S. women's national team ends its victory tour in December. Her final match will be against China on Dec. 16 in New Orleans.
"After much deliberation and talking with my friends, family, teammates and our coaching staff, I've decided to finally bring my football career to an end," Wambach said in a statement.
"While we still have more work to do for women's football, after bringing the World Cup back to the United States this summer, I'm feeling extremely optimistic about the future of our sport."
Wambach, a popular player and a vocal supporter of women's sports, led the U.S. team in scoring in every world championship she played until this summer's Women's World Cup.
"Abby is a player who has transcended our sport and her legacy as one of the world's greatest players is set forever," U.S. women's football head coach Jill Ellis said.
"I am just extremely happy that she could end her career with that elusive World Cup title and go out on top, right where she deserves to be."
In this summer's World Cup in Canada, Wambach netted the winning goal in a 1-0 victory over Nigeria in the final game of group play. The Americans defeated Japan 5-2 in the championship match, winning their first World Cup title in 16 years.
As well as having played in four women's World Cup tournaments, Wambach played in two Olympics, winning goal medals in 2004 in Athens, and 2012 in London. She missed the 2008 Olympics with a broken leg.
"It's been an amazing, wonderful ride and I can't wait to see what the next chapter of my life brings," she said.
(Reporting by Steve Ginsburg; Editing by Will Dunham and Eric Walsh)
