Greene, 33, said he planned to pursue coaching and business interests in the United States and had no regrets about his athletic career.
"It's a little sad for me but it's happy at the same time because I've had a great career. I've done a lot of great things," Greene told a news conference in Beijing. "For the last couple of years, I've had nagging injuries that have stropped my training. So I think it's better to just call it quits."
The Kansas City, Kansas, native has been of the sport's dominant figures of the past decade, setting the world record for the 100 meters in 1999 and winning the blue-ribbon sprint at the Sydney 2000 Olympics.
He also won world championship 100 titles in 1997, 1999 and 2001 — in '99 at Sevilla he also won the 200 and 4x100 relay golds in a rare triple.
The following year, he won the 100 and anchored the victorious men's 4x100 relay team at the Sydney Olympics, but did not run in the 200 after injuring himself at the U.S. trials.
His world record of 9.79 seconds stood from 1999 until 2002, when Tim Montgomery ran a 9.78 — although that time was erased when Montgomery was banned for allegedly using performance enhancing substances.
Asafa Powell set the record 9.77 in 2005.
Greene still holds the indoor 60-meter world record at 6.39 seconds.
Greene made the announcement in Beijing where he was touring facilities for this summer's Olympic Games.
He acknowledged concerns among track and field athletes over the Chinese capital's poor air quality, but said that shouldn't be a barrier to victory.
"Every athlete who is coming here is going to be going for a gold medal. And they can't let anything get in their way," Greene said.
"Every athlete is going to have to deal with" air pollution, he said. "You've got to bust the door down and take what you want."