Jacobs suffered an ankle sprain in last week's loss to the Atlanta Falcons, but the Raiders were initially hopeful he wouldn't miss game action. Gruden also ruled out safety Johnathan Abram with a knee injury Friday.
The second-year tailback was hurt late against Atlanta during an ankle tackle to end a run and hadn't participated in practice all week.
Devontae Booker will take over the team's primary backfield role. Booker has been effective when called upon this season, averaging 5.5 yards per carry and scoring three touchdowns in limited action.
Jacobs has racked up 782 yards and nine touchdowns on 206 carries this season. He's also caught 25 passes for 175 yards.
Vegas sits just outside the AFC playoff picture at 6-5 following last Sunday's defeat.