Adrian Peterson said he knew "it was something bad" the moment his left knee was hit on the first offensive play of the second half.
X-rays were negative, but an MRI revealed that Peterson tore the anterior cruciate ligament in his left knee during Minnesota's 33-26 victory over the Washington Redskins on Saturday.
The Vikings said coach Leslie Frazier will provide a further update at his news conference Monday.
The injury will likely sideline Peterson for some nine months and make it difficult for him to return for the start of next season.
"Anytime you take a blow to the knee like that, you're concerned about the ACL, MCL," Peterson said before the diagnosis. "I'm trying to stay as positive as I can."
On the play after Peterson was hurt, quarterback Christian Ponder suffered a head injury when he was sacked by Adam Carriker and London Fletcher. Ponder remained in the game for one more play — a third-down incomplete pass — before heading to the locker room.
Frazier said Ponder had "concussion-like symptoms."
The Denver Broncos lost three regulars from their secondary — including safety Brian Dawkins — to injuries during a 40-14 loss to the Buffalo Bills.
Dawkins aggravated a neck injury in the first quarter. It's the same injury that forced the 16-year veteran to sit out a 41-23 loss to New England a week earlier.
Broncos cornerback Quinton Carter did not return because of a hamstring injury, while safety Chris Harris sustained a pinched nerve while tackling quarterback Ryan Fitzpatrick in the fourth quarter.
Cardinals rookie cornerback Patrick Peterson hurt his left hamstring in a 23-16 loss to the Bengals, pulling up on the return of an interception that was nullified by penalty. The first-round pick left the game and didn't return. He wore a protective boot afterward.
"He's got a strain; it's not a tear," coach Ken Whisenhunt said. "We're fortunate that it doesn't appear to be anything long-term."
Cowboys quarterback Tony Romo was 0 for 2 before leaving Dallas' 20-7 loss to the Eagles with a bruised right, throwing hand. X-rays were negative, and oft-injured running back Felix Jones lasted just one more series, as the Cowboys were cautious with a winner-take-all showdown with the Giants looming next week.
Even coaches were getting hurt Saturday. The Giants' Tom Coughlin injured his left leg when running back D.J. Ware crashed into him on the sideline in the fourth quarter of their 29-14 win over the Jets.
Trainers made Coughlin sit on the bench for a couple of plays while they looked at his leg, but he didn't stay there long and returned to the sideline.
Afterward, Coughlin quipped, "Never felt better, never better and thank you very much for asking."
Coughlin said doctors initially felt he hurt his knee, but he believed the injury is higher on his body. He didn't give any other details.