NFL Week 1 Betting Picks: 5 Key Matchups and What to Expect

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Tom Brady #12 of Tampa Bay Buccaneers warms up before the Week 3 preseason game against the Indianapolis Colts at Lucas Oil Stadium on August 27, 2022 in Indianapolis, Indiana. Michael Hickey/Getty Images/AFP

The regular season is here! Bettors, fantasy players, general fans can all celebrate. Looking at the schedule for Week 1, there are 5 key NFL matchups that jump right out:

Here’s a look at the NFL odds and some thoughts to consider before making your bets.

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Buffalo Bills vs. Los Angeles Rams

Thursday, September 08, 2022 – 08:20 PM EDT at SoFi Stadium

Opening night on Thursday Sept. 8 will be like Christmas, with a gift wrapped in the form of the Super Bowl champion LA Rams taking on one of the AFC’s best, the Buffalo Bills.

There are some concerns for Sean McKay’s Rams. QB Matthew Stafford has been bothered by an elbow injury. The offensive line is not the same following Andrew Whitworth’s retirement. Odell Beckham is not there to catch bombs. 

The Ram defense will miss Von Miller, who signed with the Bills. He will improve a defense that was victimized by Patrick Mahomes and the Chiefs in the playoffs

Buffalo has a great passing attack and Josh Allen could be even better this season He threw for more than 4,400 yards and 36 touchdowns last year. Overlooked last year was the ground game scoring 20 touchdowns.

The Rams defense will be challenged by a team that scored 30 or more points nine times in 17 regular season games last season. I expect big things from the Bills this season and it starts with a win in Los Angeles.

NFL Pick: Bills -2.5 (-108) at Heritage Sports (visit our Heritage Sports Review)


Pittsburgh Steelers vs. Cincinnati Bengals

Sunday, September 11, 2022 - 01:00 PM EDT at Paycor Stadium

Among other games, Pittsburgh and Cincinnati should be exciting. Joe Burrow has missed a lot of preseason time and his throws may not be where they should be. Plus T.J. Watt will be in his face all day.

Pittsburgh starts Mitch Trubisky and he could feel the pressure in his first Steeler start.

Running backs could be big in this game. Najee Harris and Joe Mixon should shine; perhaps field possession will lead to fewer big plays.

Cincinnati held Pittsburgh to 10 points in both games last season. With Burrow likely not 100 percent, an under could be worth a look.

NFL Pick: Under 44.5 (-108) at Heritage Sports


San Francisco 49ers vs. Chicago Bears

Sunday, September 11, 2022 - 01:00 PM EDT at Soldier Field

The 49ers and Bears have an interesting QB matchup with Trey Lance starting now.

Over in the Midwest, Justin Fields looked good in the preseason. Chicago scored 17 points or fewer in half of their games last season. San Francisco will be stronger at home and Lance will take time to succeed. Another under here.

NFL Pick: Under 41.5 (-108) at Heritage Sports


New England Patriots vs. Miami Dolphins

Sunday, September 11, 2022 - 01:00 PM EDT at Hard Rock Stadium

The Patriots and Dolphins meet in the AFC East. The Dolphins have improved the offense and Jaylen Waddle has a great teammate in Tyreek Hill. It will be tough to stop them. Miami improved its offensive line and running game, and Tua Tagovailoa looks a lot more confident under new coach Mike McDaniel. 

Miami swept New England last year, holding the Pats an average of 20 points a game in the two contests. The Patriots have an injury-plagued receiving corps and Miami is much better this season. I like Miami to prevail.

NFL Pick: Dolphins -3 (-108) at Heritage Sports


Tampa Bay Buccaneers vs. Dallas Cowboys

Sunday, September 11, 2022 - 08:20 PM EDT at AT&T Stadium

The Bucs and Cowboys meet in a game that will draw big TV numbers. Tom Brady missed 11 days of preseason time but that won’t matter. He has a good receiving corps that has improved with Julio Jones added.

The problem is the offensive line, which has been killed by injuries already. He may not have as much time to throw.

Dallas has had injuries within its receiving corps, so Dak Prescott and Ezekiel Elliott could feel additional pressure. This could be an intense battle. 

Todd Bowles wants to win his head coaching debut badly. Brady will find a way to get it done. The Bucs won last year’s meeting, 31-29. I expect less offense this time around.

NFL pick: Buccaneers -1 (-110) at BookMaker (visit our BookMaker Review)

*The line and/or odds on picks in this article might have moved since the content was commissioned. For updated line movements, visit BMR’s free betting odds product.