The Swans were leading 40-8 late in the first quarter at the SCG on Saturday and riding a wave of momentum, with every positive act generating massive cheers from the home fans.
Then Mills' right knee gave way as he attempted to corral Lions ball-carrier Will Ashcroft, and immediately the crowd held their breath.
Mills rose gingerly to his feet and was helped off the ground by two Swans trainers, accompanied by a large round of sympathetic applause as he made his way down the race.
The Swans soon confirmed Mills would play no further part in the match, before the 29-year-old reappeared on the bench with crutches and gave the crowd a thumbs-up when he was shown on the big screen.
A serious knee injury could rule Mills out for the rest of the finals series and even a large portion of next season.
It comes amid speculation over the playing futures of the five Swans teammates - including star trio Isaac Heeney, Chad Warner and Nick Blakey - who were suspended for breaching club behavioural standards last month.
Mills had earned plenty of kudos for his leadership after the Swans were engulfed by turmoil in the fallout from the Pullman Hotel scandal, which led to the club-imposed player bans.
The latest setback could be another significant injury for Mills, who missed most of the 2024 season after hurting a shoulder in a 'Mad Monday'' wrestling contest with a teammate.
Mills returned to action late in 2024 and played in Sydney's first final, but injured a hamstring and was sidelined when the Swans lost to Brisbane in the season decider.
On Saturday, the Lions also suffered a first-quarter casualty, with Noah Answerth hobbling off with an ankle issue shortly after Mills went down. Answerth received attention and returned to play.
Cheers of "Sydney, Sydney" Â rolled down from the stands before the game, as fans responded to calls from players and officials to back the understrength team.
The Swans kicked six of the first seven goals and led by 30 points at halftime.
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