The precociously talented 32-year-old will feature in the Women's National Premier League and act as a club ambassador.
It is a coup for the former National Soccer League giants, who have made no secret of their desire to resume a place in the top tier of Australian football.
Women's football has been a key plank of their proposal.
Earlier this season, the club commenced mixed training sessions for their elite men's and women's teams.
The signing of De Vanna shows they are prepared to back up their intent with action.
The West Australian confirmed her signing on Friday night.
"Glad to announce that I'm officially a SMFC player and will be the clubs women's football ambassador. A club with history and ambition," she tweeted, showing a picture of her holding the club's shirt.
De Vanna is one of Australia's all-time leading goalscorers and one of the most decorated players to pull on a gold shirt.
She captained Melbourne City to the 2015/16 W-League title but had a late start to the 2016/17 campaign with rivals Canberra United.
In United's semi-final loss to City, she was involved in an off-the-ball incident with City player-coach Jess Fishlock, striking the Welsh playmaker behind the ball.
South Melbourne will be the three-time W-League winner's seventh Australian club home. She has also had stints in England, Sweden and the United States.