Docherty went down injured in a tackle in the first quarter of Carlton's dramatic one-point opening-round win over Brisbane at the Gabba on Friday night.
He returned to play before being substituted in the second quarter, with the injury a sour ending to the Blues' dramatic victory.
Scans on Saturday confirmed a ruptured ACL and meniscus tear in Docherty's right knee, in the latest setback of a career marked by a horror run with illness and injury.
An All-Australian half-back in 2017, Docherty previously tore back-to-back ACLs - in his left knee - that wiped out his 2018 and 2019 season.
Docherty, 30, underwent chemotherapy for testicular cancer in 2020, then had a recurrence in 2021, which prematurely ended that season.
The much-loved defender and former Blues co-captain made an inspirational return in 2022, then played a key role in last season's run to a preliminary final.
"Football becomes almost insignificant when you consider all Sam has endured and overcome over the last few years," Carlton football boss Brad Lloyd said in a statement.
"This news simply isn't fair, but as Carlton people we love Sam dearly - we will support him through this so he can return to the field when he is ready.
"It won't just be the entire Carlton family behind Sam, I can safely say the football world no doubt will be as well.
"His impact on our side will certainly be missed on the field, however his impact on his teammates and on the selfless environment we are creating will continue to be profound right throughout the club.
"Sam will throw his heart and soul into helping his teammates get the best out of themselves because that is just the person he is - and he knows we'll be right alongside him through every step of his rehabilitation."
Docherty, who has played 168 games, is contracted until the end of next season after signing a new deal last year.
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