McKendry suffered the injury to his right knee during the Panthers win over South Sydney on Saturday.
The 28-year-old, who has torn the same ACL in 2016 and 2017, will now seek specialist medical advice about his best options for recovery.
“It’s unbelievably sad news for Sam and his family,” Panthers Executive General Manager Phil Gould AM said on the club’s website.
“He has worked so hard on overcoming this injury before.
“It’s a huge blow for our club as well. Sam really looked like he was getting back to his best.
“As always we will ensure Sam gets the best of medical advice and care. But sometimes this game just isn’t fair.”