The Bucs placed the running back on the physically unable to perform list on Tuesday afternoon, meaning Williams won't be available for the first six games. After that, a three-week window opens during which Williams can begin practicing and the Bucs will have to decide whether to activate him or put him on the injured reserve list for the remainder of the season.
The 2005 NFL Rookie of the Year suffered a torn patellar tendon in a Week 4 game against Carolina last season. Coach Jon Gruden has been praising Williams' recovery, but the injury often takes more than a year to heal.
The Bucs likely will open the season with Earnest Graham as the starting running back and Warrick Dunn and Michael Bennett as the backups.
In trimming the roster to 75 on Tuesday, the Bucs also put cornerback Sammy Davis (hip) on injured reserve and waived receiver Paris Warren and two injured players, linebacker Antoine Cash (neck) and safety Donte Nicholson (knee).
If Cash, taken from the field on a stretcher after colliding with a teammate making a tackle during Saturday's preseason loss to Jacksonville, and Nicholson clear waivers, they automatically will be placed on IR.
Pat Yasinskas covers the NFL for ESPN.com. Information from The Associated Press was used in this report.