Buffalo Bills' defender Damar Hamlin was given CPR on the field after he collapsed following a tackle on a Bengals opponent.
Medics worked on Hamlin for 16 minutes on the Paycor Stadium turf in Cincinnati before an ambulance took the 24-year-old to hospital.
The match, which was set to be a crucial clash just two weeks before the NFL playoffs, was suspended after the injury.
Hamlin had collided with Bengals receiver Tee Higgins after the Cincinnati player had caught a pass from quarterback Joe Burrow.
Hamlin then got to his feet, appeared to adjust his face mask with his right hand, and then fell backward about three seconds later and lay motionless.
The Bills later confirmed Hamlin suffered a cardiac arrest before his heartbeat was restored on the field.
He remains in UC Medical Centre where his condition is listed as critical.
The ambulance was on the field four minutes after Hamlin collapsed, with many players in tears, including cornerback Tre'Davious White.
The quarterbacks — Buffalo's Josh Allen and Cincinnati's Burrow — embraced.
When Hamlin was taken off the field, the Bills gathered in prayer.
Hamlin's uniform was cut off and he appeared to be getting CPR from medical personnel. ESPN reported on its telecast that Hamlin was also given oxygen.
"No one's been through this," longtime NFL quarterback Troy Aikman said on the ESPN telecast. "I've never seen anything like it, either."
Hamlin collapsed at 8:55 pm local time and the game was suspended 21 minutes later. Players walked off the field slowly and into their locker rooms.
The aftermath of the injury was reminiscent of when Bills tight end Kevin Everett lay motionless on the field after making a tackle on the second-half opening kickoff in Buffalo's 2007 season-opening game against the Denver Broncos.
Everett sustained a spinal cord injury that initially left him partially paralysed.
The 24-year-old Hamlin spent five years of college at Pitt — his hometown — and appeared in 48 games for the Panthers over that span.
He was a second-team All-ACC performer as a senior, was voted a team captain and was picked to play in the Senior Bowl.
He was drafted in the sixth round by the Bills in 2021, played in 14 games as a rookie and then became a starter this year once Micah Hyde was lost for the season to injury.
A tweet from the Pitt football account was simple and clear: "Damar Hamlin is the best of us. We love you, 3," the tweet said, referring to Hamlin by his college jersey number. "Praying for you."
AP