The Pittsburgh Steelers head to Highmark Stadium in Orchard Park this Sunday afternoon to take on the Buffalo Bills in Week 1 of the 2021 NFL season, so here’s the best Steelers vs. Bills betting pick along with the latest odds update. 

According to Bovada Sportsbook, the Bills are 6.5-point home favorites with a total of 48.5 points, while the Steelers are listed as +240 moneyline dogs. These two AFC foes meet for the third straight year, and the Bills have gone 2-0 straight up and ATS against the Steelers over the past two years.  

The Steelers have a new look 

The Pittsburgh Steelers enter the new season with high hopes, although they have an entirely new offensive line. Last season, the Steelers have recorded a paltry 1351 rushing yards, as their ground game was dead last in the NFL, averaging 3.6 yards per carry.

This time around, the Steelers have a new face in their backfield, too. Rookie Najee Harris has been a dominant force at Alabama, and the Steelers hope he’ll be a key factor in 2021. In his last 26 games with the Crimson Tide, Harris has recorded 3419 yards from scrimmage and 50 touchdowns.

Ben Roethlisberger returns for his 18th season after leading the Steelers to the 12-4 record in 2020. Pittsburgh leaned on Big Ben way too much, and the Steelers suffered a heavy 48-37 defeat at Cleveland in the AFC wild-card game, as Roethlisberger threw for 501 yards, four touchdowns, and four interceptions. Pittsburgh’s defense struggled with injuries in the second half of the 2020 season which was another reason for their early playoff exit.

The Bills sit at +1100 to win the championship   

While the Pittsburgh Steelers are +3000 underdogs to win the Super Bowl LVI, the Bills are considered as the third-strongest fave, as only Kansas City at +450 and Tampa Bay at +550 have better chances than Buffalo.

The Bills will have a tall task to retain the AFC East crown, as their divisional rivals have done a great job in the offseason. Still, Buffalo returns all its key players from the 2020 season, and the Bills have dominated the vast majority of their rivals last year, finishing with a 13-3 record.

Josh Allen and Steffon Diggs will continue to lead the way for the Bills’ offense. Allen completed 69.2 percent of his passing attempts for 4544 yards and 37 touchdowns in 2020, while Diggs led the NFL with 1535 receiving yards. However, the Bills will have to find the right balance after averaging just 107.6 rushing yards per game last season (20th in the NFL).



  • 2-5 ATS in the last seven games overall 
  • 0-5 ATS in the last five games against the AFC East 


  • 9-2 ATS in the last 11 games overall 
  • 6-2 ATS in the last eight games against the AFC
  • 5-2 ATS in the last seven games played in September

Pittsburgh Steelers vs. Buffalo Bills Pick

There’s a big question mark in this matchup, as we are about to see the Steelers’ brand-new offensive line. The Bills are a good defensive team, though their run D finished 17th in the NFL last season. On the other side, Pittsburgh’s defense will have to step up and disrupt the Bills’ pass protection, and it’s hard to say if they can do it in Week 1.

I don’t feel comfortable with a 6.5-point spread, but the Bills should come out on top at home, so I’ll take them to cover. Last season, Buffalo outlasted Pittsburgh 26-15 as a 2-point home fave with a total of 48.5 points.

Pick: Take Buffalo Bills -6.5 at -110     

The Total:

The under is 5-1 in the last six encounters between the Steelers and Bills, and it is 17-5 in Pittsburgh’s previous 22 games overall. On the other hand, the over is 8-3-1 in the Bills’ last 12 outings at any location.

I’m expecting both teams to lean heavily on their signal-callers. If we get a lot of action through the air, this one’s going in the over.

Pick: Go over 48.5 points at -110