Williams' left ankle was caught underneath as Sweezy made the block on a 2-yard run by Marshawn Lynch. He was down on the field for a few minutes before being helped off by a pair of trainers, putting very little weight on his left leg.
After the game, Niners head coach Jim Harbaugh said Williams' ankle might be broken, but that he hadn't seen X-rays yet.
San Francisco tight end Vernon Davis left the game in the fourth quarter with a strained hamstring and it was announced he would not return. Davis finished with three receptions for 20 yards.
The Niners also lost rookie safety Eric Reid, who left the game in the second quarter with what was later deemed a concussion. Reid was hurt on a hit over the middle when he tackled Seattle receiver Sidney Rice.
Information from ESPN.com's Terry Blount and The Associated Press was used in this report.