Lynch, who had been seen limping after several plays in the third quarter, finally stayed down after a 1-yard completion to wide receiver Emmanuel Sanders with 6 minutes, 22 seconds remaining in the third quarter.
The Broncos trailed 21-0 when Lynch left the game. He was visibly emotional on the sideline after exiting.
"I was just more frustrated with having another injury and having to come out of the game after recovering from another injury," Lynch said. "And then the first game back I hurt my ankle."
It was Lynch's first start of the season after he had suffered a right shoulder injury in the Broncos' Aug. 26 preseason game against the Green Bay Packers. Lynch missed two months of practice with the injury and had just returned to the field earlier this month.
Overall, Sunday was a struggle for Lynch, as he was 9-of-14 passing for 41 yards with a deflected ball for an interception before leaving. He had also been sacked four times.
Lynch had been given the green light by the Broncos coaching staff this past week to run his way out of trouble if he was able. He had 20 yards on two runs; both of those runs were in the first quarter.
Trevor Siemian, who was benched as the starting quarterback after a three-interception night in an Oct. 30 loss to the Kansas City Chiefs, entered the game and threw TD passes to Cody Latimer and Bennie Fowler III in the fourth quarter.
Lynch said he is hoping he can return Sunday against Miami.
"I'm not sure. I'm hoping I can get back out there sometime this week and play next week,'' Lynch said. "Obviously I want to play, but I don't know the extent of the injury right now.''