NFL Week 1 Best Bets: Top Picks for Sunday's Games
The greatest Sunday of the year is upon us, as NFL Week 1 gets things rolling for the 2026 season on September 13, meaning we'll have NFL football on our screens every Sunday through the rest of 2026. It's a beautiful feeling, and after Patriots vs Seahawks and 49ers vs Rams whet our appetites, it's time to lock in for this huge 12-game slate on Sunday. With 12 games and an infinite number of markets to work through, the slate can be pretty daunting. But that's why Pickswise is here! Our experts have combed through every matchup and picked out their NFL best bets for Week 1.
Let's break down our four top NFL picks for Sunday, while you can also get access to our NFL predictions for every game all season long. A reminder that our experts posted a 311-251-4 record in the 2025 season, for a profit of +90.1 units!
NFL Week 1 Best Bet: Jacksonville Jaguars -8.5 over Cleveland Browns (-110)
Odds available at bet365 at time of publishing.
The Cleveland Browns will open the 2026 season on the road in Jacksonville against a long former divisional foe in the Jaguars. The Browns’ preseason wasn’t exactly pretty, and they’re starting Deshaun Watson at quarterback out of the gate, so it’s hard to get excited about Cleveland at this moment. Offensive line play could be slightly better, but they’re pretty much starting fresh there across the entire unit, including a rookie at left tackle. Not to mention, two of their top three receivers are rookies. That’s a ton of inexperience to play with on the road in Week 1 with an absolutely inept quarterback under center, to put it bluntly.
Jacksonville’s Josh Hines-Allen, Antonio Johnson and Ventrell Miller are all difference makers on the defensive side, while Travon Walker has tallied almost 25 sacks over the last three seasons. Cleveland’s offensive line will certainly be put to the test here.
On the other side, Cleveland's Jared Verse should at least be a decent consolation for Myles Garrett’s departure with his 12 sacks in his first two NFL seasons, while the addition of linebacker Quincy Williams adds experience alongside the young star in Carson Schwesinger. However, the interior defensive line of Mason Graham and Maliek Collins raises some questions regarding how good this stop-unit can be against the rush, and I question the secondary outside of Denzel Ward. That said, even Ward had a tough year in 2025, pulling in just one interception and grading below replacement level by PFF.
I’m expecting Trevor Lawrence to be able to pick apart this defense. Jacksonville has a stable of wide receivers that can leave the Cleveland secondary looking clueless, especially with the added element of Lawrence’s mobility. The Browns didn’t see too many mobile quarterbacks last year – Lamar Jackson didn’t run as much – so I’m really keeping my eye on that dynamic.
At the end of the day, the Jaguars are a bona fide playoff team playing at home against a struggling Browns organization that is working in a new and first-time NFL head coach with Watson under center, while their best and most exciting player is no longer on the team. As far as the side goes, I could only lay it with the Jags.
Pick and analysis from expert handicapper Sam Avellone.
Get more Browns vs Jaguars picks, including a prediction on the total
NFL Week 1 Best Bet: Atlanta Falcons +5.5 over Pittsburgh Steelers (-115)
Odds available at DraftKings Sportsbook and bet365 at time of publishing.
Both of these teams enter this interconference matchup at Acrisure Stadium with brand new head coaches. Former Packers coach Mike McCarthy is reunited with QB Aaron Rodgers to lead a Pittsburgh squad coming off a 10-7 season and AFC North title.
The Steelers host the Falcons, who closed with an 8-9 mark and bring in ex-Browns head man Kevin Stefanski to get Atlanta over the hump. The Falcons signed former Dolphins QB Tua Tagovailoa, who gets the opening-week start and tries to improve on a 4-1 record in his five Week 1 starts.
Atlanta won its final four games of 2026, including three victories by three or fewer points. RB Bijan Robinson ranked second in the league in rushing yards after contact (1,133) and tied for third in 10+ yard rushes (36). The Falcons put together a perfect 5-0 against the spread mark in five road/neutral contests, including three outright wins.
Meanwhile, the Steelers went 3-1 straight-up and against the spread as a home favorite, although Rodgers averaged 195.7 passing yards at home. Pittsburgh won at Atlanta in the 2024 season opener, 18-10 as 4.5-point underdogs, but the Steelers failed to score a touchdown and kicked six field goals.
The Falcons probably have the three best offensive weapons on the field with Robinson, WR Drake London, and TE Kyle Pitts, Sr. as Tua is the wild card here to make it work with them.
Pick and analysis from expert handicapper Kevin Rogers.
Get more expert analysis in our Falcons vs Steelers predictions
NFL Week 1 Best Bet: Houston Texans +1.5 over Buffalo Bills (-112)
Odds available at DraftKings Sportsbook at time of publishing.
The Buffalo Bills open their 2026 season on the road in Houston, and the number here is about as tight as it gets, with the Bills sitting as small favorites. I like the value on the home dog. Houston's defense has been a genuine problem for Josh Allen dating back before DeMeco Ryans ever took over as head coach, and that front, paired with a secondary that's healthy to open the year, gives the Texans a real shot to keep this one within a field goal or steal it outright.
Buffalo also enters this game with some defensive uncertainty of its own. The Bills moved on from defensive-minded head coach Sean McDermott and promoted former offensive coordinator Joe Brady to the top job, which means less continuity on that side of the ball than Buffalo has had in years.
A shakier Bills defense against a Houston offense that should be fully healthy for the first time in a while, with Stroud, Nico Collins and a retooled offensive line all back, sets up better for the Texans than the market price suggests.
The head-to-head betting trends back this up too: Houston has covered in six of the last 10 meetings between these two teams. With Buffalo breaking in a new-look coaching staff and Houston catching a full number at home, I'll take the points with the Texans.
Pick and analysis from expert handicapper Luke Lindholm.
Get more Bills vs Texans picks for this crunch AFC matchup
NFL Week 1 Best Bet: LA Chargers -9.5 over Arizona Cardinals (-105)
Odds available at FanDuel Sportsbook at time of publishing.
When away from the house, it will ruin your day if your chargers aren’t working correctly. LA’s front office must have thought the same thing after last season, and they brought in a lot of help to make sure they stay plugged in. Mike McDaniel came over as the new offensive coordinator. Coach Jim Harbaugh brought in answers to plug up the holes in the offensive line. They brought back 10 starters on defense and added arguably one of the best linebackers in the draft - first-round pick Akheem Mesidor.
The Chargers went 11-6 and made the playoffs last year. It was the third time in their last four seasons. The offensive success that got them there was led by Justin Herbert. Last year, he often found himself in trouble and was sacked 60 times, which left his offensive line tied for 29th in pressure rate allowed. The breakdown in protection did help him improve his run game, as he rushed for 498 yards and two touchdowns. His troubles were mostly because right tackle Rashawn Slater missed the entire season and tackle Joe Alt was out for 11 games. Both of those problems have been dealt with and improved upon. They even added Jake Slaughter at center, who was said to be one of the best in his second-round draft class.
10 out of their 11 starters return on defense. Herbert is back and healthy, and so is his favorite running back, Omarion Hampton. They fixed the problems on the offensive line, so Herbert will have more time to focus downfield. Ladd McConkey and Quentin Johnston are back and healthy, while new tight end addition David Njoku will also provide a great target for Herbert. Add McDaniel as OC, and I feel you have a solid playoffs-bound team that will prove to be too much for the Cardinals; the same team who lost their final nine games last year, five of them by 17 points or more. Getting the Chargers at minus a TD and field goal feels like a steal.
Pick and analysis from expert handicapper Aaron Taylor.
Get NFL stats, trends and more in our full Cardinals vs Chargers predictions
NFL Week 1 Picks
Check out our expert NFL predictions for every Week 1 matchup below:
- Bears vs Panthers prediction
- Browns vs Jaguars prediction
- Buccaneers vs Bengals prediction
- Falcons vs Steelers prediction
- Saints vs Lions prediction
- Bills vs Texans prediction
- Ravens vs Colts prediction
- Jets vs Titans prediction
- Packers vs Vikings prediction
- Commanders vs Eagles prediction
- Cardinals vs Chargers prediction
- Dolphins vs Raiders prediction
- Cowboys vs Giants SNF prediction
- Broncos vs Chiefs MNF prediction
