The NFL season is underway as the Arizona Cardinals open the season with the Buffalo Bills on Sunday at Highmark Stadium. We're live from Orchard Park, New York, as we share our NFL odds series and make a Cardinals-Bills prediction and pick.

The Cardinals had another bad season, going 4-13. Now, they hope to improve. Kyler Murray leads a new-look offense and will be ready to roll. Ultimately, he tossed 1,799 yards, 10 touchdowns, and five interceptions in limited action last season. Running back James Conner rushed 208 times for 1,040 yards and seven touchdowns. Meanwhile, tight end Trey McBride had 81 catches for 825 yards and three scores.

The defense will need to do better. Dennis Gardeck led the pass rushers with six sacks. Also, Kyzir White had 90 tackles before tearing his triceps. Jalen Thompson led the defense with four interceptions.

The Bills went 11-6 last season, winning the division in the final weekend. Unfortunately, they bowed out to the Kansas City Chiefs (again) in the postseason.

Josh Allen played well, passing for 4,306 yards, 29 touchdowns, and 18 interceptions. Additionally, he rushed 111 times for 524 yards and eight scores. James Cook rushed 237 times for 1,122 yards and two touchdowns.

The Bills lost both Stefon Diggs and Gabe Davis. Now, they will rely on a new core. Khalil Shakir is the only main receiver who returns. After catching 39 passes for 611 yards and two touchdowns, he looks to do more this season. Tight end Dalton Kincaid also looks to raise the bar after catching 73 passes for 673 yards and two scores. Meanwhile, the Bills acquired Curtis Samuel and Chase Claypool while also drafting Keon Coleman.

The defense took some hits this offseason. Regardless, they will still have one of their top pass rushers as Leonard Floyd returns after notching 10.5 sacks.

Here are the NFL odds, courtesy of FanDuel. 

NFL Odds: Cardinal-Bills Odds

Arizona Cardinals: +6.5 (-110)

Moneyline: +235

Buffalo Bills: -6.5 (-110)

Moneyline: -290

Over: 47.5 (-102)

Under: 47.5 (-120)

How to Watch Cardinals vs. Bills

Time: 1 pm ET/10 AM PT

TV: CBS

Stream: fuboTV (Free Trial)

Why The Cardinals Could Cover The Spread/Win

The Cardinals need to start fast. Unfortunately, that is the only way they can steal this one. For the Cardinals to win this game, they need the offense to step up.

Murray needs to improve. He is 2-1-1 in Week 1 games, so he has some good experience starting the season. But can he take the next step and help lead the Cardinals to a major upset? Conner needs to find space and run the ball efficiently to get Murray some room.

Marvin Harrison Jr. makes his NFL debut and hopes to make an instant splash. Amazingly, he destroyed numerous defenses while representing Ohio State. Harrison will face a Bills' defense in transition. Thus, expect him to be a major part of the action.

The defense can only get better after being one of the worst units in the NFL. However, facing Allen will be the toughest test to start the season. This is where edge rusher Darius Robinson comes in.

The Cardinals will cover the spread if Murray can jettison them to an early lead. Then, the defense must contain Allen and prevent him from getting time to throw or run.

Why The Bills Could Cover The Spread/Win

The Bills will look different without Diggs and Davis. Yet, they still have one of the most talented rosters in the NFL. Additionally, they still have Allen.

Allen is only 3-3 in Week 1 games. While he is one of the best quarterbacks in the NFL, he struggles to start his seasons. Allen will need to do well as Joe Brody returns to run the offense. Ultimately, that means running the ball will be a heavy emphasis. Getting the receivers involved will also be integral.

Taylor Rapp, Mike Edwards, and Cole Bishop will try to fill the gaps in the defense after Jordan Poyer and Micah Hyde depart. Thus, this unit will be under a lot of pressure to contain fast receivers.

The Bills will cover the spread if Allen can direct the offense to numerous successful drives early. Then, the defense must stop Murray and ruin Harrison's NFL debut.

Final Cardinals-Bills Prediction & Pick

The Bills lead the head-to-head series 7-5. However, their last matchup occurred on November 15, 2020, when the Cardinals edged out the Bills 32-30. The Bills have won four in a row in this series and have never lost to the Arizona Cardinals at Orchard Park. Consequently, the Cards have not beaten the Bills in New York since they were the St. Louis Cardinals in 1971. This one could be similar.

The Cardinals are 36-50-2 in Week 1 games. Meanwhile, the Bills have stumbled in Week 1 games recently, going 2-2-1 over the past five games. Buffalo gets a good test to showcase their new talent and what they can do. Frankly, the Bills have too much firepower for this Cardinals' team. We can see them winning by at least a touchdown.

Final Cardinals-Bills Prediction & Pick: Buffalo Bills: -6.5 (-110)