Week three of the NFL season will see the Arizona Cardinals travel to Buffalo to take on the Bills in their first road contest of the season.

The Cardinals are coming off the 40-7 victory over the Tampa Bay Buccaneers, while the Bills try to rebound from their 37-31 loss against the New York Jets.

The last time these two teams squared off, the Bills defeated the Cardinals in a overtime thriller in 2012 in University of Phoenix Stadium. This time around, the Cardinals will be on a mission, a mission that has been 45 years in the making.

The last time the Cardinals won a game in Buffalo, they were still playing in St. Louis. They defeated the Bills 28-23 on Halloween of 1971. Since then, the Cardinals have played the Bills three more times in Buffalo, losing all three of their meetings.

Injury Report

Cardinals:

Justin Bethel CB Questionable

Kareem Martin LB Doubtful

Evan Mathis G Out

Robert Nkemdiche DT Questionable

Frostee Rucker DT Doubtful

Bills:

Colt Anderson S Out

Charles Clay TE Questionable

Cordy Glenn OT Out

Greg Salas WR Questionable

Sammy Watkins WR Questionable

Cardinals on offense

Arizona Cardinals wide receiver Larry Fitzgerald scores a touchdown as New England Patriots cornerback Logan Ryan defends. (AP Photo/Rick Scuteri) (The Associated Press)
Arizona Cardinals wide receiver Larry Fitzgerald needs to continue his strong start to the season. | Photo: AP Photo/Rick Scuteri

Last week, the Cardinals offense returned to form against a Buccaneers defense, throwing for 315 passing yards. This week they will be try to duplicate those numbers going up against a Bills defense that is ranked 23rd in the NFL.

Last week against the Jets, the Bills did not blitz much, allowing Jets quarterback Ryan Fitzpatrick to pick the Bills defense apart. Carson Palmer could do the same. Even if the Bills defense brings the blitz more, there was no quarterback better than Palmer when throwing against the Bills a year ago.

Bills coach Rob and Rex Ryan enjoy the man to man set. Stephon Gilmore, Ronald Darby, Nickell Robey-Coleman, and Aaron Williams will be given the task to slow down a very talented Cardinals receiving core, including running back David Johnson. Larry Fitzgerald has been Palmer’s favorite target these first couple of weeks of the season, hauling in 13 catches for 158 yards and three touchdowns.

The Cardinals should see some improvement in the run game as well. David Johnson has been great, getting most of the Cardinal carries. Chris Johnson and Andre Ellington will need to step up when given the opportunity. Chris Johnson got more carries last week and had 54 yards and a touchdown. Johnson and Johnson look to keep the ground game rolling.

Bills on offense

Buffalo Bills running back LeSean McCoy (25) runs the ball against the New York Jets. Mandatory Credit: Brad Penner-USA TODAY Sports (Brad Penner)
Buffalo Bills running back LeSean McCoy is going to be key. | Brad Penner-USA TODAY Sports

The Bills changed offensive coordinators last week, firing Greg Roman and promoted Anthony Lynn. The Bills will try to play power football and pound the ball with running back LeSean McCoy. Tyrod Taylor has mobility, giving him the ability to make plays with his feet. When the Cardinals played the New England Patriots, Jimmy Garoppolo had four carries, running for a first down against the Cardinals defense.

The Cardinals will devote everything they have to stop the Bills running game. A solid defensive line, a good linebacker group that includes mobile linebacker Deone Bucannon and a strong safety with double digit tackles in his first two games in Tony Jefferson are just a few resources.

If the run game isn’t working, the Bills will need to have success in the passing game to beat the Cardinals. Receivers Sammy Watkins and Greg Salas will not be at 100 healthy. Marquise Goodwin and Robert Woods will have to get around the ball hawking Cardinals secondary. Patrick Peterson will be on Watkins all day, with defensive player of the week Marcus Cooper getting his first start on the opposite side. Tyrann Mathieu will also be tested, trying to eliminate the deep threat.

Game Prediction

The Cardinals will end their 45-year winless streak in Buffalo with a win on Sunday. The Cardinals should have few problems moving the ball down the field and getting points against a bottom ranked Bills defense.

Injuries to the Bills key playmakers should limit the Bills offense. With McCoy, Watkins and Salas being banged up, it will put a lot of pressure for other guys to step up. Both the ground and passing games might struggle because of it.

The Cardinals should continue to put together wins as they enter the portion of the schedule against less favorable opponents.