The 22-year-old will miss the rest of the season after going down in the second quarter of Sunday's draw with Port Adelaide at Ikon Park.
Guerin has played 15 games since crossing from Melbourne ahead of the 2021 season.
Carlton sit ninth after three rounds with a 1-1-1 record.
"Maddy has worked exceptionally hard to develop her game and earn her spot in our midfield group," Carlton women's football manager Brett Munro said.
"She was just starting to hit her stride so it's incredibly disappointing to see Maddy sidelined for the rest of the year, but she has our entire football club supporting her and we'll work with her through her rehab."
It comes only days after Blues forward Mia Austin suffered a horrific leg injury at training.
Austin broke her fibula and suffered an ankle syndesmosis injury during a match simulation session with her teammates on Thursday night.
The setbacks to Guerin and Austin continue a devastating run of injuries in the AFLW.
Gold Coast vice-captain Jaime Stanton, Eagle Kellie Gibson, Brisbane defender Lily Postlethwaite, St Kilda's Jayde Van Dyk, GWS defender Pepa Randall and Hawthorn's Tamara Luke have suffered ACL tears this year.
Star Port Adelaide recruit Gemma Houghton will miss at least six weeks after she underwent ankle surgery on Tuesday.
Western Bulldogs utility Brit Gutknecht broke her tibia and fibula when an opponent fell across her leg.
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