Entering his third year as a Blue, and his 10th within league circles, Williams was expected to play a prominent role in Michael Voss' lineup, dividing his team between half-back and the engine room.
However, as first reported by 7News' Mitch Cleary, these plans have gone awry, with the tattooed Blues' campaign now in tatters.
Carlton's Head of Football, Brad Lloyd, confirmed Cleary's reports on Saturday afternoon, stating that Williams had already been booked in for surgery and would miss the season.
“These incidents are so unfortunate and we are all feeling for Zac, he could not have done any more this pre-season to get himself ready for the year,” Lloyd said in a club statement.
“He will undergo surgery to repair his ACL and from there, we will put a rehabilitation program in place for him over the next 12 months.
“He has had more than his fair share of bad luck with injury Zac but in that time he has built up a lot of resilience, which he will no doubt tap into, as we all support him on his road to recovery from here.”
Brought to Carlton as a high-priced recruit ahead of the 2021 season, Williams has been hampered throughout multiple portions of his Princes Park stay, with calf and Achilles complaints keeping him to just 25 appearances across the last two years.
Williams still has a further three seasons to run on his lucrative contract.
Williams thanked those who had sent him messages of support on Sunday, though a social media post on Instagram.
"Would like to say thanks to everyone from my family, friends, teammates, Carlton faithful for all the support over last 48 hours," Williams wrote.
"Very grateful for all the care shown, and no doubt that care will get me through next 12 months to come back bigger and better! Super excited to see my teammates play some really exciting football this year. No doubt they will dominate this year. Go Blues."
The diagnosis is set to see the Nerranderrra native become the latest Blue to injure his cruciate ligament, following Caleb Marchbank and David Cuningham, who have been left battling identical injuries in recent times.
Despite spending pockets of the summer training with the midfield group, Williams' injury is also likely to see veteran Sam Docherty return to playing out of the defensive arc to begin the year.
Any void left by Docherty in midfield will be felt doubly, with star Blue Sam Walsh not expected to return from back surgery until at least a month into the home-and-away season.
The Blues will be out to snap a finals drought that stretches back to 2013, a feat they narrowly failed to achieve last season after missing out on a place in the eight by 0.6 of a percentage point.