Wicketkeeper-batter Matthew Wade has joined the team for the white-ball tour of South Africa after Maxwell suffered a "minor aggravation" to his left ankle at training.
The injury is on the same leg that Maxwell broke last year but scans have cleared him of serious damage.
However, Australia don't want to take any risks with the 34-year-old, ruling him out of the three-match T20 series, which begins on Wednesday (Thursday AEST).
Maxwell was already going to miss the five-match ODI series against South Africa that follows the T20 component in order to return home for the birth of his first child.
The ODI World Cup starts on October 5 and runs through to November 19.
"We are taking a precautionary approach, given Glenn was heading home next week in any case," Australia selector Tony Dodemaide said.
"We will monitor Glenn's recovery with a view to him being available for the three-match ODI series in India in advance of the World Cup."
Wade, who hasn't played for Australia since last year's doomed T20 World Cup title defence, is a ready-made middle order replacement.
The 35-year-old signed a contract extension with the Hobart Hurricanes on Monday, tying him to the BBL franchise until 2026.
"Wadey is a world class performer and is and is fit and ready to go, having this week completed his commitments with the London Spirit in The Hundred," Dodemaide said.
Pat Cummins (wrist), Mitchell Starc (groin), Steve Smith (wrist), Josh Hazlewood, Cameron Green and David Warner are among the big names who will miss the T20 series in South Africa.
Mitch Marsh has been named as skipper, filling the gap left by the retired Aaron Finch.
Australia will pick their preliminary squad for the ODI World Cup next week, with the final 15 player squad to be confirmed by September 28.
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