Australia's all-time leading goalscorer suffered the injury during English club Chelsea's warm weather training camp in Morocco.
It will almost certainly rule the 30-year-old out of the Paris Olympics, should Australia qualify as expected via next month's two-legged tie with Uzbekistan.
The Olympics, where Australia are hoping to medal, start in 200 days but the football tournament begins on July 24, two days earlier.
It is another devastating blow for superstar striker Kerr after a calf injury rocked her home Women's World Cup campaign last year.
"Considering how hard Sam has worked over the past six months to return to play, this news is a devastating blow for everyone," Matildas coach Tony Gustavsson said.
"With her ability to lead by example, Sam's guidance and influence on the team is significant and, as a result, this will be an incredible loss for the national team.
Sam Kerr would have been a key figure in Australia's planning to claim a medal at the Olympics. (AP PHOTO)
"Our focus now is on ensuring she has all the support she wants and needs to navigate recovery and rehab," Gustavsson concluded.
Kerr has already been ruled out of the second half of Chelsea's WSL and European Champions League campaigns, and Australia's AFC Women's Olympic qualifiers round three series against Uzbekistan next month.
The World Cup semi-finalists need only to win that two-leg tie - against a team ranked 47th in the world, 35 places below the Matildas - to qualify for Paris.
The Games soccer tournament takes place from 24 July - 10 August, but it is rare for a player to return from an ACL injury with less than eight months rehabilitation, and it often takes longer.
In Kerr's absence, the likes of Mary Fowler, Caitin Foord and Emily van Egmond will be among central striker options, along with emerging attacker Amy Sayer.Â
Like at the World Cup, vice-captain Steph Catley appears poised to step up as skipper in Kerr's absence.
Catley and her Matildas teammates were quick to post messages of support for their injured captain.
No words 💔 Here with you every single step — Steph Catley (@stephcatley) @samkerr1 ������ https://t.co/t8vQuLdaQlJanuary 7, 2024
Kerr is the latest leading female player to suffer the injury, which seems more prevalent in the women's game and is belatedly the subject of research into why this is.Â
Ellie Carpenter was out for eight months after injuring her ACL in the 2022 Champions League final. (EPA PHOTO)
Ellie Carpenter, Kyah Simon, Chloe Logarzo, Elise Kellond-Knight and Holly McNamara are among Australian players to have suffered ACL injuries in recent years.Â
England's Beth Mead and Leah Williamson, Vivianne Miedema of the Netherlands and France's Marie-Antoinette Katoto were among a string of stars to miss the World Cup while Spain's Alexia Putellas had only just returned to playing and is still to regain her former level.
Kerr, runner-up to Spain's Aitana Bonmati at the Ballon d'Or awards last year, is Australia's record goalscorer with 69 in 128 matches.
Chelsea said she "will be assessed by a specialist in the coming days and then begin her rehabilitation with the club's medical team".
Sam Kerr has been a multiple trophy winner with Chelsea, including the 2022 Women's Super League. (AP PHOTO)
Kerr has scored 99 goals in 128 games for the club, winning the WSL Golden Boot twice, four league titles and three FA Cups - scoring in each final, but is out of contract this summer.Â
She was recently joined in London by her partner, American player Kristie Mewis, who joined WSL rivals West Ham United.
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