"Today, with a wide range of feelings, I'm announcing my retirement from basketball," the future Hall of Famer said on Twitter. "It's been a fabulous journey. Way beyond my wildest dreams."
One of the game's most decorated international players, Ginobili, 41, was a four-time NBA champion, a two-time NBA All-Star and an Olympic gold medalist for Argentina.
A second round draft pick of the Spurs in 1999, he played in 1,057 games, averaging 13.3 points and 3.8 assists.
Ginobili helped the Spurs win NBA titles in 2003, 2005, 2007 and 2014.
He also was a gold medallist with Argentina in 2004 and won EuroLeague Finals most valuable player honours in 2001.
The swingman, a fan favourite in San Antonio, was under contract for 2018-19, but he said in April that he was weighing what's next in his career.
"As I've done it the last two or three seasons, I'll sit back, relax and, after two or three months, see if I feel retired or not," Ginobili said. "I like to let it season a little bit, to see how I feel.
"I'm not the type of guy who makes decisions on the fly, and when you are upset, hurt or whatever."
Ginobili averaged 8.9 points, 2.2 rebounds and 2.5 assists per game in 20 minutes per game last season for the Spurs, who were eliminated in the playoffs by the champion Golden State Warriors.