Mumford had been weighing up his future since the Giants' finals exit in September.
It was expected the 35-year-old would call it quits but delayed the announcement until Friday.
Mumford, who started his AFL career at Geelong in 2008, became one of the most consistent, physical and intimidating big men in the game.
He bows out after 216 games with the Cats, Sydney Swans and the Giants, after initially retiring in 2017 due to a serious foot injury.
After a year as GWS' ruck coach in 2018, where he also started a professional boxing career, Mumford felt fit enough to return to the field in 2019.
"Over 200 AFL games in the physical manner and the position in which Shane played is a wonderful achievement," GWS football boss Jason McCartney said.
"From the rookie list to 13 seasons at the elite level, including a premiership, Shane has achieved a lot in his career.
"He arrived at our club in just our third season, and he has had a monumental impact on our club."
Mumford will revert back to his role as a ruck coach at the Giants next season.
He says he will cherish playing in the Swans' memorable 2012 grand final triumph over Hawthorn.
"My time on the football field has come to an end for now," Mumford said.
"I'm incredibly proud of all that I've achieved across my career in the game including winning the ultimate, a premiership, in 2012."
Despite playing through significant pain during his three-season comeback and struggling to play every week, Mumford will now leave a huge hole in the Giants' team.
GWS are hopeful Braydon Preuss can overcome his injury battles after arriving from Melbourne ahead of last season.
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