The 29-year-old Chelsea star picked up the calf problem in training, and the news is a huge blow for her country.
To highlight how much of a blow it is, England legend Ellen White said: "This is [Erling] Haaland missing for Norway or [Lionel] Messi for Argentina."
Ker will miss the co-hosts' opening Group B clash against the Republic of Ireland at Stadium Australia on Thursday.
Australia's all-time record scorer, will also be absent against Nigeria on 27 July.
She will be hopeful of returning prior to her side's match of the group stages against Canada on July 31.
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The Australia national team confirmed she will not feature in their opening two matches of the competition.
"Sam Kerr is unavailable tonight after she picked up a calf injury at training on matchday minus-one," a statement read on Twitter.
"Sam will be unavailable for the next two matches with the Matildas medical team to re-assess her following our second group-stage match."
Ker is a formidable figure both on and off the pitch for her nation, managing 63 goals in 120 matches.
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She also has three successive domestic doubles to her name with Women's Super League champions Chelsea.
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