The Parramatta playmaker suffered the injury during Australia's 24-22 win over New Zealand in the tournament opener on Thursday night in Sydney.
He attempted to play on but eventually left the field less than two minutes into the second half.
While initially believed to be a calf issue or hairline fracture, scans following the match revealed Moses had suffered an unspecified "high-grade muscle tear", meaning his World Cup campaign is over.
It's a blow to the Kangaroos, who are already missing Nathan Cleary with a serious leg injury, with Moses the Kangaroos' strongest last-tackle kicker.
Moses switched allegiance to play for Australia at this tournament after captaining Lebanon at the 2022 World Cup.
Kangaroos coach Kevin Walters said the 32-year-old was understandably disappointed to miss the remainder of the campaign.
"Mitch made a wonderful contribution to our World Cup preparations during the camp in Sydney and very bravely tried to play through the injury until he eventually had to come from the field on Thursday night," Walters said in a statement on Saturday.
"He is naturally disappointed at the outcome today, and the fact that he tried to stay out there when he was clearly injured shows just what it means to him to represent his country and play in the Kangaroos jersey."
It continues a horror run at representative level for the play-making veteran.
During this year's State of Origin series Moses suffered a hamstring strain at training was forced out of the NSW line-up for the opening match of the series.
In 2025 a calf strain in camp also ruled him out of Blues contention for Game II while a year earlier a left foot fracture kept him out of the series opener.
Canberra five-eighth Ethan Strange, one of three Australian shadow players, will replace Moses in the 23-man squad.
The 22-year-old hasn't played a Test for the Kangaroos but represented the Australian Prime Minister's XIII against Papua New Guinea a year ago.
Strange made his State of Origin debut this year when he replaced the injured Moses in the NSW squad.
Australia's next pool match is against Fiji in Brisbane next Sunday night.
Walters is set to rotate his squad with Sam Walker and Tom Dearden the new halves pairing.
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