Sam Bradford was running out of bounds when a shove sent him tumbling to the ground.
Reggie Wayne was wide open when he turned to catch a low throw and crumbled to the turf.
Two seemingly harmless plays turned out to be quite costly. Bradford and Wayne each tore an anterior cruciate ligament in their knees and will miss the rest of the season.
Bradford's injury is a devastating blow to the St. Louis Rams, who will turn to backup quarterback Kellen Clemens.
Wayne's injury seriously dampened the Indianapolis Colts' spirit after a big win over Peyton Manning.
''I have great respect for what he does on the field, but just as genuine concern for him as a person,'' Clemens said of Bradford, who was hurt when he was pushed by Carolina's Mike Mitchell late in the fourth quarter of a loss to the Panthers.
Bradford tore his left ACL, which coach Jeff Fisher said was already in a brace. The former No. 1 overall pick had 14 touchdown passes and just four interceptions in his fourth season.
Wayne tore his right ACL in the fourth quarter of a victory over Denver. The soon-to-be 35-year-old wide receiver had played in 189 consecutive games. Wayne led his team with 38 catches and 503 yards this season. In 13 seasons, all with the Colts, he has 1,006 receptions, 13,506 yards and 80 TD catches.
''Looking back at it again today, there was really no one within 30 yards of him,'' quarterback Andrew Luck said. ''He probably would have scored if I actually give him a decent ball. I feel somewhat responsible for the whole thing. I think I feel sick to my stomach about it a little bit.''
The Chicago Bears also suffered big losses Sunday. Quarterback Jay Cutler will miss at least the next four weeks after tearing a muscle in his groin during a 45-41 loss to Washington. Pro Bowl linebacker Lance Briggs will be out for around six weeks after sustaining a small fracture in his left shoulder.
Veteran Josh McNown will replace Cutler. Pro Bowl cornerback Charles Tillman also left the game with a knee injury for the Bears.
In other injury news:
Houston Texans Pro Bowl linebacker Brian Cushing is out for the season with a left knee injury that will require surgery. Cushing, who tore his left ACL last season, was injured in the third quarter of a loss at Kansas City during a low block by running back Jamaal Charles.
The Green Bay Packers lost tight end Jermichael Finley to a significant neck injury in their win over the Browns. Finley needs more tests to determine the severity.
Philadelphia Eagles quarterback Nick Foles sustained a concussion in a loss to Dallas. Meanwhile, Michael Vick is still recovering from a hamstring injury that forced him to miss the past 2 1/2 games.
Washington Redskins strong safety Reed Doughty suffered a concussion when the Bears attempted an onside kick in the fourth quarter.
Atlanta Falcons running back Steven Jackson, who has missed the past four games with a hamstring injury, is expected to practice on Wednesday.
AP Sports Writers R.B. Fallstrom in St. Louis and Michael Marot in Indianapolis contributed to this report.
Online: AP NFL site: http://pro32.ap.org/
Follow Rob Maaddi on Twitter: https://twitter.com/AP-RobMaaddi