Tennessee quarterback Marcus Mariota broke his right leg in a loss to the Jaguars, ending his season early for a second straight year.
And Mariota was just one of the quarterbacks knocked out of games with injuries Sunday. Browns quarterback Robert Griffin III went to the locker room with a concussion as Cleveland got its first win this season, while Jets quarterback Bryce Petty hurt his left shoulder in a loss to New England.
Mariota was hurt when sacked late in the third quarter by rookie Sheldon Day with the Titans quarterback scrambling to throw on first down. Day grabbed Mariota around the ankles, and the quarterback stayed down, immediately signaling to the sideline.
The quarterback, who missed the final two games of the 2015 season with a sprained knee, pounded on the ground several times.
Trainers placed an air cast on his right leg before Mariota was lifted onto a cart and taken to the locker room.
Titans coach Mike Mularkey said Mariota will need at least six weeks to recover. That leaves veteran Matt Cassel as Tennessee's quarterback after a 38-17 loss that severely damaged Tennessee's playoff hopes.
The Jaguars had both running backs T.J. Yeldon (ankle) and Chris Ivory (hamstring) leave the game with injuries.
Cleveland ended its winless skid, beating San Diego 20-17. Yet Griffin was taken to the locker room with a concussion after being sacked for the seventh time.
Griffin, who was replaced by rookie Cody Kessler, already missed 11 games this season with a broken bone in his left shoulder.
Browns cornerback Joe Haden also went to the locker room with an injured neck, the two-time Pro Bowler hurt apparently while tackling on a running play.
San Diego linebacker Denzel Perryman had a leg injury in the fourth quarter and was taken from the field on a cart.
Petty hurt his left shoulder in a 41-3 loss to New England, a week after bruising his chest in the Jets' loss to Miami.
The Jets also lost tight end Austin Seferian-Jenkins to an injured hamstring in the first half, and he did not return. Runnng back Khiry Robinson finally was active for the first time this season and left with a leg injury.
Defensive lineman Leonard Williams returned after leaving the game in the third quarter with an injured chest.
The Green Bay Packers got a brief scare in the third quarter when quarterback Aaron Rodgers stayed down on the ground for a couple of minutes after a sack.
Trainers checked Rodgers, who walked to the bench where he flexed his neck. He returned on the next series.
But Packers cornerback LaDarius Gunter left with an injured elbow in the second quarter, while right tackle Bryan Bulaga hurt his shoulder in the fourth.