Fletcher tore a knee ligament in practice Wednesday and Amendola was to have surgery Thursday for the left elbow he dislocated in the season opener.
Amendola led the team with 85 receptions last season. The Rams had been hopeful he'd return after the team's bye week, but he had a setback in his rehab and got a second medical opinion on Wednesday in Dallas.
"Initially it might seem like a drop-off, but we expect these guys to step up and play," coach Steve Spagnuolo said Wednesday in anticipation Amendola would be out for an extended period. "We miss Danny, there is no question about that."
Fletcher was hurt in a collision with wide receiver Mike Sims-Walker, who had what was believed to be a minor shoulder injury.
Fletcher is the second cornerback the Rams have lost for the season. Ron Bartell went on IR after sustaining two fractures in his neck in the opener.
The Rams (0-4) have been hard-hit at the position.
A third cornerback, Jerome Murphy, was knocked out for the year with an ankle injury in training camp and three others, seventh-round pick Mikail Baker, Dionte Dinkins and Tim Atchison, are on injured reserve.
Cornerback Marquis Johnson could be returning from the physically unable to perform list after the Oct. 16 game at Green Bay. Johnson has been rehabbing from a knee injury sustained last season.
The starters against the Packers could be Justin King, who had an interception last week against Washington, but gave up three touchdown passes the previous week against the Ravens, and 36-year-old Al Harris.
Recent pickup Rod Hood and Josh Gordy, promoted from the practice squad two weeks ago, may get playing time against the Packers.
"Well, I think it's possible," defensive coordinator Ken Flajole said before the severity of Fletcher's injury was known. "We'd have to be smart about what we called.
"We couldn't ask them to learn everything that we've had in since the beginning of training camp because there's just too much volume and too short of a time."