The Redskins have placed running back Chad Simpson and safety Anderson Russell on injured reserve and signed running back James Davis from the practice squad.
Simpson suffered a broken foot during pre-game warm-ups in Sunday's game at Tennessee.
Russell, an undrafted rookie, suffered a knee ligament tear during a punt return in the first quarter.
It's a disappointing end to the season for Simpson and Russell, two young players trying to establish themselves in the league.
Russell had been called up from the practice squad on Nov. 8 when Chris Horton went down with a foot injury.
Davis joined the Redskins' practice squad on Oct. 27 after he was released by the Cleveland Browns.
Davis, regarded as a classic one-cut runner who fits Shanahan's scheme, had been considered to be called up from the practice squad in recent weeks as the team's running backs struggled with injuries.
"He's a talented player," head coach Mike Shanahan said of Davis.
Davis entered the NFL as a sixth-round draft choice by the Cleveland Browns in 2009.
He played in six games last year as a reserve with the Browns. He had 13 carries for 24 yards and four receptions for five yards in limited action.
Davis, a native of Atlanta, starred at Clemson from 2005-08. He led the Tigers in rushing with 3,881 yards and a school-record 47 touchdowns.