It is the same right knee injury he suffered in round eight last year, meaning a season-ending reconstruction on the anterior cruciate ligament that caused him to miss out on the Lions' premiership.
The 31-year-old small forward had made a successful return in the pre-season and was pushing for a senior berth.
But McCarthy reported swelling and soreness in the knee at training last week, and scans revealed the horrible news.
While the Lions did not say how long McCarthy will be sidelined, he is unlikely to play this season.
"It's incredibly disappointing and heartbreaking for Linc, his family and everyone at the Brisbane Lions to see him injure his ACL again," Lions general manager of football Danny Daly said on Tuesday.
"But we have all been so impressed with the way Linc dealt with his last ACL injury and how committed he was to return, so we have no doubt he will tackle this injury with the same attitude.
"In the meantime, everyone at the club will rally around Linc and support him through this process, and he is a fan favourite as well, so no doubt they will be sending their support for Linc."
McCarthy has played 151 AFL games since his 2012 debut at Geelong, starting with the Lions in 2019.
Brisbane have had a spate of ACL tears, with Keidean Coleman, Darcy Gardiner and Tom Doedee all sidelined last season with the injury.
Gardiner tore his ACL in the same round-eight match as McCarthy.
Doedee is yet to debut for the Lions after moving from Adelaide, suffering his third ACL rupture a year ago.
Meanwhile, the Swans will be without Aaron Francis and Indhi Kirk with concussion for their grand final rematch against Brisbane at the SCG on Saturday.
Tall defender Riak Andrew will also miss with a shoulder injury.
32°C