"It had nothing to do with the spike," Fisher said. "His groin was real tight and we just didn't want to subject him to it. I didn't think he'd be 100 percent."
Jackson said he thought he'd be able to re-enter the game but said the groin tightened on him.
Griffin led the Redksins (1-1) to a 21-6 lead, but the Rams came back thanks to the pass-catching of Amendola. The receiver tied an NFL record 12 first-half receptions, and caught a 1-yard TD pass to cut the lead to 21-13 at the half.
Bradford had second-half scoring passes of 34 yards to Brandon Gibson and 1 yard to Matt Mulligan.
Griffin ran for two touchdowns and passed for a third for Washington (1-1).
The Redskins got a final shot after DeAngelo Hall recovered running back Daryl Richardson's fumble at the Washington 37 with 2:40 to go. Billy Cundiff, though, was wide right and well short on 62-yard field goal attempt with 1:13 left.
The Rams took the lead on Bradford's TD pass to Mulligan on the first play of the fourth quarter, and Richardson ran it in on a 2-point conversion for a 24-21 lead. Mulligan had partially blocked Sav Rocca's punt to give the Rams the ball at the Washington 24 four plays earlier.
Griffin, who looked like a veteran in his NFL debut last week in leading the Redskins to a win over New Orleans, scored on runs of 5 and 7 yards. He also threw a 68-yard touchdown pass to Leonard Hankerson.
Jackson spiked the ball after getting ruled short of the goal line on a third-down carry from the 1. It came a play after the Rams successfully challenged a lost fumble call on Jackson.
Fisher then pulled the franchise's career leading rusher, who spent most of the rest of the game by himself on the sideline with his helmet in hand, and went with Richardson and fellow rookie Isaiah Pead. A team spokesman said Jackson was not injured.
Amendola had a rough start, fumbling after a 13-yard catch on the Rams' first snap, with Josh Wilson returning it 30 yards for his fifth career defensive touchdown. He recovered nicely, matching the first-half NFL record set by the Colts' Reggie Wayne in 2007, while tying his career best game total in the process and setting a personal game-best with 133 yards receiving.
The Redskins lost defensive end Adam Carriker and outside linebacker Brian Orakpo to injuries early in the first quarter, while Rams offensive tackle Rodger Saffold was helped off with a right knee injury.
Carriker injured his right knee on the Redskins' second snap on defense. He removed his jersey and tossed gloves to the stands, contradicting a team statement that his return was questionable.
The return of Saffold, a surprise starter who was hospitalized with a neck strain in Detroit after the opener, also was questionable.
Orakpo and Saffold were hurt on the same play. Orakpo stripped Rams quarterback Sam Bradford and Saffold recovered the fumble and carried it 7 yards, but crumpled to the turf on the tackle.
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Washington 14 7 7 0 28
St. Louis 3 13 7 8 31
Was • J.Wilson 30 fumble return (Cundiff kick), 14:49.
StL • FG Zuerlein 39, 9:05.
Was • Griffin III 5 run (Cundiff kick), :19.
StL • FG Zuerlein 33, 8:17.
Was • Hankerson 68 pass from Griffin III (Cundiff kick), 6:19.
StL • Amendola 1 pass from Bradford (Zuerlein kick), 1:58.
StL • FG Zuerlein 42, :02.
StL • Gibson 34 pass from Bradford (Zuerlein kick), 10:23.
Was • Griffin III 7 run (Cundiff kick), 5:27.
StL • Mulligan 1 pass from Bradford (D.Richardson run), 14:55.
Attendance • 53,979.
First downs 18 23
Total Net Yards 373 452
Rushes-yards 29-176 27-151
Passing 197 301
Punt Returns 1-(-3) 4-29
Kickoff Returns 4-53 1-12
Interceptions Ret. 1-0 1-5
Comp-Att-Int 20-29-1 26-35-1
Sacked-Yards Lost 1-9 2-9
Punts 6-40.0 3-54.3
Fumbles-Lost 0-0 3-2
Penalties-yards 11-96 7-60
Time of Possession 28:36 31:24
Rushing • Washington, Morris 16-89, Griffin III 11-82, Royster 1-4, F.Davis 1-1. St. Louis, D.Richardson 15-83, Jackson 9-58, Bradford 3-10.
Passing • Washington, Griffin III 20-29-1-206. St. Louis, Bradford 26-35-1-310.
Receiving • Washington, Morgan 5-50, Moss 3-14, Paul 3-13, Hankerson 2-68, A.Robinson 2-40, F.Davis 2-14, Royster 2-7, Helu 1-0. St. Louis, Amendola 15-160, St.Smith 3-39, Gibson 2-53, Kendricks 2-25, D.Richardson 2-19, Mulligan 2-14.
Missed Field Goals • Washington, Cundiff 62 (SH).