Safety Adrian Wilson blitzed untouched and leveled the second-year quarterback, slamming him to the ground.
The Bills went on to lose 41-17.
Edwards, who had directed Buffalo to a 4-0 record, lay on the ground for several minutes before being helped to the sideline. He was carted off the field, and the Bills reported a short time later that he had a concussion.
Edwards completed a 13-yard pass to James Hardy just before he was hit by Wilson.
Wilson, a game-time decision because of a hamstring injury, called for help from the Buffalo sideline right after the play.
"I looked to see if the ball was completed, then he didn't get up," Wilson said. "I know the situation that happened with Anquan [Boldin] last week, so it was just a scary situation whenever you see a guy just laying there and not moving. So I just wanted to help out."
Former starter J.P. Losman took Edwards' place.
"I just came from Trent," coach Dick Jauron said in his postgame news conference. "Trent was responding, but he was still a little groggy. Hopefully, he'll be fine as time goes by here. It's a good time to have a bye."
Buffalo has next weekend off, then is home against San Diego on Oct. 19.
Wilson, rushing from the left side of the Arizona defense, hit Edwards hard just below the face.
"I don't think it was helmet-to-helmet but I've only seen one replay on the big board," Jauron said. "There are other things involved in any hit on a quarterback so we'll see where that one goes."
Edwards' neck was being iced and would continue to be iced on the airplane ride home, the coach said.