Williams confirmed the news on Twitter.
"Regret to inform yall I will be out for the season with a torn acl," Williams wrote. "Not how I saw things playing out but in the end I will be fine and (this) is just another obstacle I will have to climb to get back. Looking forward to the challenge!! Love all true fans your prayers are (much) appreciated."
Williams became a household name last season following his string of gaffes in the NFC championship loss to the New York Giants. He remained a Jim Harbaugh favorite and a major contributor on special teams in 2012, returning punts and kicks along with Ted Ginn. Williams also saw his role in the passing game grow, accounting for 14 catches 212 yards and a touchdown this season.
Williams' absence might lead to rookie A.J. Jenkins seeing time at the No. 4 wideout spot. Jenkins has yet to play this season after a troubling summer, so Harbaugh will have to decide how much trust he's willing to place in the young pass-catcher.
Follow Marc Sessler on Twitter @MarcSesslerNFL.