Wildcats coach Sean Miller said Wednesday that news of Williams' season-ending surgery "is beyond disheartening."
Williams has had issues with the knee since high school, missing his junior season after having surgery to correct a congenital condition.
The same knee flared up a few times last season when Williams missed six games.
He still was a Pac-12 All-Freshman Team Honorable Mention, averaging 11.4 points, 2.8 rebounds and 3.4 assists in 26 games, including 21 starts.
In a statement, Williams said he's "overcome obstacles before in my life and will work with our strength and medical staffs to overcome this one."