The game will take place in Glendale, AZ, where the Cardinals have defeated Seattle, Philadelphia and Miami already this year. Buffalo leads the all-time series 5-4, but Arizona won the last meeting between the two teams by 24 points.
They key to this game seems to be how well Buffalo's offensive line can play against the Cardinals' front seven, not only in protecting quarterback Ryan Fitzpatrick, but also in creating holes to establish a running game.
For the Cardinals to win this game and go to 5-1, they will need big plays from the following players.
Cardinals quarterback Kevin Kolb is averaging 31 pass attempts per game. But if the Cardinals can't get anything out of the running game, he might throw it 50 times on Sunday.
With Beanie Wells and Ryan Williams both out with injuries—Williams for the remainder of the season—the Cardinals need one of their relatively unknown backs to step up. William Powell will get the first opportunity to do so, but Alfonso Smith and LaRod Stephens-Howling will probably get some work as well.
Powell only has nine yards rushing on three carries on the season, but he did lead the league in rushing during the preseason. Buffalo comes into this game ranked 30th in rush defense, giving up about 172 yards a game. There should be room for Powell to run, and that will take some of the pressure off of Kolb.
Paris Lenon/Stewart Bradley
Linebacker Paris Lenon is currently listed as questionable for this game, and if he can't go, Stewart Bradley will be asked to take his place.
Whoever gets the start will need to aid in attacking the Bills' running game, which is the team's best chance to leave the desert with a victory. Fred Jackson and CJ Spiller will share the load and look to get the Buffalo ground game going. Lenon or Stewart will have to help out Darnell Dockett, Calais Campbell and Dan Williams in shutting it down.
Peterson will draw the assignment of Bills receiver Stevie Johnson. Johnson leads the team in receptions (21), targets (45) and receiving yards (234). The rest of the Bills receivers have combined for just 31 receptions.
If Peterson can bottle Johnson up, Fitzpatrick will be forced to choose between the rest of his options at the position, TJ Graham, Donald Jones and Brad Smith. That's a scenario the Cardinals defense would likely get the best of.
Both guys have already played up the matchup, making it even more intriguing.
Who wins this game?
If the Cardinals want to keep the momentum of their strong start, this is a game they have to win. They are at home against a Bills team that doesn't want to start falling too far back in the AFC East, so they will get their best shot.
If the Cardinals can get something on the ground and protect Kolb, they will win this game. Larry Fitzgerald is poised to have a huge day.
Kolb has been sacked 17 times in the last two games, and now Mario Williams will be on the other side. Williams has been a disappointment since signing a huge free-agent contract to come to Buffalo, with just 1.5 sacks on the season. But with the woes of the Cardinals offensive line this season, he could turn that around in a hurry.
If the Bills can gain big chunks of yardage on the ground and get pressure on Kolb, they will walk away with the upset.
It will be one of Sunday's more hotly-contested games, and there's a good chance it goes down to the wire.
Pick: Cardinals win 24-23 with a late touchdown.