The superstar halfback is unlikely to play again this year unless the Roosters reach the grand final, and even then, that would require a rapid recovery.
Return from syndesmosis surgery typically takes six to eight weeks, though players have come back in five, with the title decider exactly five weeks away on Sunday.
Walker went for scans after being crunched by Kulikefu Finefeuiaki in Saturday's 26-12 loss to top-four rivals the Dolphins.
The 24-year-old's absence shapes as a significant hurdle for the fourth-placed Roosters, who looked to have their best chance at a premiership this decade.
Walker has been in career-best form this season and was clearly the Maroons' best player in his first State of Origin series this year.
The injury will turn Daly Cherry-Evans' NRL swan song into a rescue mission, with the England-bound veteran expected to shift back into the No.7 jersey.
Hugo Savala would likely then replace Cherry-Evans at five-eighth, having slotted into the halves when Walker went down against the Dolphins.
Cherry-Evans, 37, has spent recent years as the main man at Manly, having led them to eight finals series and being a premiership-winning rookie in 2011.
Walker's injury comes after an ACL rupture ruled him out of the finals two years ago, with Trent Robinson's men making the preliminary final then.
But his latest injury is only one concern for a Roosters side that has dropped from top of the ladder into fourth spot over the past two weeks.
Consecutive losses to Wests Tigers and the Dolphins has left their gritty defeat of Penrith three weekends ago as a distant memory.
Unless the Roosters defeat arch-rivals South Sydney next weekend, they could fall into fifth spot to finish the regular season and miss the crucial double chance in finals.
No team has won the premiership from fifth or lower on the ladder since 1995.
The Dolphins were superb on Saturday but the Roosters were well below their best, letting the game get away from them in the 20 minutes before halftime.
Equally concerning was the way the Dolphins beat them out after the break, going 26-6 up before Walker's injury.
"I can't believe we were down by that much and got jumped at halftime, and missed the physical kick as well," coach Trent Robinson said.
"Overall it's really disappointing for us on that performance. We're still creating opportunities but not finishing them."
In better news, the Roosters were confident hooker Reece Robson had not suffered an injury after leaving the field late.
Daniel Tupou could also return on the wing next week, effectively replacing Savala in the backline.
15°C