Williams, who entered the game as the Broncos' leader in carries and rushing yards, stayed down on the field after a 1-yard loss on the first play of the second half. Athletic trainers checked his right knee before he was helped to the injury tent on the Broncos' sideline.
Williams was not able to put his full weight on his leg as he was helped to the sideline. A few minutes later he was taken to the Broncos' locker room on a cart and ruled out for the remainder of the game.
Williams left the Broncos locker room in Allegiant Stadium on crutches as some of his teammates offered quiet encouragement. Broncos coach Nathaniel Hackett said Williams will be sent for an MRI on Monday morning.
"We're still evaluating,'' Hackett said. " ... We want to be sure we get MRIs and get a feel there.''
"Obviously seeing Javonte go down, that hurt,'' quarterback Russell Wilson said. "Hopefully he'll be OK.''
Outside linebacker Randy Gregory will also be sent for an MRI on Monday after he suffered a right knee injury with just under six minutes remaining in the game on a 9-yard scramble by Raiders quarterback Derek Carr.
Gregory, who signed a five-year, $70 million contract with the Broncos in March, had knee surgery after the 2021 season when he was still with the Cowboys and had shoulder surgery after he signed with the Broncos. It isn't known if he injured the same knee Sunday against the Raiders.
Mike Boone replaced Williams in the Broncos' lineup right after Williams went down. Melvin Gordon III had split time with Williams over the first three games of the season, but Gordon fumbled in the second quarter and the Raiders' Amik Robertson returned it 68 yards for a touchdown.
It was Gordon's fourth fumble of the season -- the Broncos have lost two of them. Gordon did get some carries on the Broncos' next possession.
But if Williams' injury forces him to miss significant time, it will force the Broncos to make an adjustment. Williams, a second-round pick by the Broncos in the 2021 draft, came into the game with 175 yards on 37 carries over the season's first three weeks and was the Broncos' second-leading receiver with 15 catches over those three games.
He had 28 yards on 10 carries Sunday before his injury.