Wilson's fierce hit on the third play of the game sent the Bills quarterback to the locker room with a concussion, and the Arizona Cardinals went on to emphatically hand Buffalo its first loss of the season, 41-17.

"I had my mind made up this morning that I was going to play," Wilson said. "Coach (Ken) Whisenhunt asked me if I had a role, what would it be. I said I could go on third down. That was my role."

Kurt Warner bounced back from an awful weekend at the Meadowlands to pick apart the Bills' defense with short passes, completing 33 of 42 for 250 yards with no interceptions. Nine Arizona receivers had catches. The Cardinals had no lost fumbles or interceptions.

"We're a tough team to beat when we don't turn the ball over," said Whisenhunt, whose team had seven turnovers a week earlier in a 56-35 road loss to the New York Jets.

Warner threw three interceptions and fumbled the ball away three times in that game, so he spent the week hanging onto the football around the house.

"I was actually chasing my kids around and I had two hands on the football," the father of seven said, "or they were chasing me around trying to simulate the Buffalo Bills."

Rookie Tim Hightower had touchdown runs of 17 and 2 yards for the Cardinals, who stand alone atop the NFC West.

The Cardinals (3-2), without standout receiver Anquan Boldin, amassed 373 yards against what had been one of the stingier defenses in the league. Buffalo's offense contributed, too, fumbling the ball away three times in Bills territory, resulting in 17 Arizona points.

Buffalo had rallied in the fourth quarter to win its last three. The Bills were down 31-17 after three in this one, and it only got worse from there.

Coach Dick Jauron painted as positive a face on the loss as he could.

"I'd much rather go into the bye week 5-0 than 4-1," he said, "but I'm willing to bet there's not a lot of people in this room that thought we'd be 4-1."

J.P. Losman, who wanted an offseason trade after losing his job to Edwards, was 15-of-21 for 220 yards, most of them on an 87-yard touchdown pass to Lee Evans.

"I try to mentally prepare every game like I'm going to go in," Losman said. "Today, I was put to that test - quite early - which is unexpected. But that's my job right now."

With Boldin out as a result of the vicious helmet-to-helmet hit by the Jets' Eric Smith, his replacement Steve Breaston caught seven passes for 77 yards.

"I knew with Anquan being out we'd have to rely on a lot of other people," Breaston said, "and I think a lot of people stepped up."

Larry Fitzgerald had seven catches for 52 yards, including a pair of touchdowns, and rookie Early Doucet caught six for 42 yards in his pro debut.

In its two home games, Arizona has outscored Miami and Buffalo by a combined 72-17.

After ringing up 35 points in a second-half rally against the Jets, Arizona scored on all four of its first-half possessions to go up 24-14 at the break. The first three went for touchdowns, giving the Cardinals eight TDs in nine possessions.

Very early, it looked to be a long day in the desert for the Bills.

Wilson blitzed untouched and leveled Edwards, slamming the second-year quarterback onto his back. Edwards lay on the ground for several minutes before being helped to the sidelines.

"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."

Wilson immediately signaled to the Buffalo sideline that Edwards was hurt.

"I know the situation that happened with Anquan last week," Wilson said, "so it was just a scary situation whenever you see a guy just laying there and not moving."

Two plays later, Losman and Marshawn Lynch botched a handoff that gave Arizona the ball at the Bills 38. Warner's 2-yard TD pass to a wide open Fitzgerald gave Arizona the lead, and the Bills never pulled even again.

Two of the first-half touchdowns came on a 14-play, 80-yard drive and a 12-play, 78-yard drive. Together, the possessions consumed just under 13 minutes.

Turnovers set up the Cardinals' 10 fourth-quarter points.

Notes: Arizona is 8-2 at home since Whisenhunt took over a year ago. ... The Cardinals had 28 first downs, 19 in the first half. ... Buffalo entered the game allowing teams to convert on third downs an NFL-best 19 percent of the time. Arizona converted 9-of-13, 6-of-6 in the first half.