After three weeks of preseason action, Week 1 of the 2022 NFL regular season is officially here, and we have a tremendous matchup on Thursday night between the Bills and Rams. We also have a 14-game slate on Sunday beginning at 1 p.m. ET, giving bettors many opportunities to bet on multiple sides, totals, money lines, and player props.
Week 1 features several big games (Bills-Rams, Bucs-Cowboys, Chiefs-Cardinals) and storylines (Baker Mayfield and Russell Wilson playing their former teams, new coaches making their debuts). However, there will also be some intrigue surrounding a couple of other games, such as Jaguars-Commanders and Saints-Falcons. These games might not be on the radar of bettors, but there could be value to had on the moneyline or when it comes to player props.
Please remember that the odds and lines will move throughout the week as we get updates on various injuries across the league. Therefore, there could be some opportunity for closing line value (CLV) in a few games leading up to kickoff. Below, we take a look at the latest odds for Week 1 from Caesars Sportsbook and provide a few best bets that need to be on your radar.
NFL WEEK 1 PICKS: Against the spread | Straight-up predictions
NFL odds Week 1
Odds courtesy of Caesar's
| Game | Spread |
| Buffalo Bills at Los Angeles Rams | BUF -2.5 |
| Cleveland Browns at Carolina Panthers | CAR -2.5 |
| New England Patriots at Miami Dolphins | MIA -3 |
| Philadelphia Eagles at Detroit Lions | PHI -4 |
| Baltimore Ravens at New York Jets | BAL -7 |
| San Francisco 49ers at Chicago Bears | SF -7 |
| Indianapolis Colts at Houston Texans | IND -7 |
| Jacksonville Jaguars at Washington Commanders | WSH -2.5 |
| New Orleans Saints at Atlanta Falcons | NO -5.5 |
| Pittsburgh Steelers at Cincinnati Bengals | CIN -6.5 |
| Kansas City Chiefs at Arizona Cardinals | KAN -6 |
| Green Bay Packers at Minnesota Vikings | GB -1.5 |
| Las Vegas Raiders at Los Angeles Chargers | LA -3 |
| New York Giants at Tennessee Titans | TEN -5.5 |
| Tampa Bay Buccaneers at Dallas Cowboys | TB -2.5 |
| Denver Broncos at Seattle Seahawks | DEN -6.5 |
NFL money lines Week 1
| Game | Moneyline |
| Buffalo Bills at Los Angeles Rams | BUF -135 |
| Cleveland Browns at Carolina Panthers | CAR -135 |
| New England Patriots at Miami Dolphins | MIA -178 |
| Philadelphia Eagles at Detroit Lions | PHI -205 |
| Baltimore Ravens at New York Jets | BAL -305 |
| San Francisco 49ers at Chicago Bears | SF -320 |
| Indianapolis Colts at Houston Texans | IND -345 |
| Jacksonville Jaguars at Washington Commanders | WSH -140 |
| New Orleans Saints at Atlanta Falcons | NO -235 |
| Pittsburgh Steelers at Cincinnati Bengals | CIN -278 |
| Kansas City Chiefs at Arizona Cardinals | KC -250 |
| Green Bay Packers at Minnesota Vikings | GB -125 |
| Las Vegas Raiders at Los Angeles Chargers | LA -178 |
| New York Giants at Tennessee Titans | TEN -260 |
| Tampa Bay Buccaneers at Dallas Cowboys | TB -145 |
| Denver Broncos at Seattle Seahawks | DEN -267 |
NFL over/unders Week 1
| Game | Over/Under |
| Buffalo Bills at Los Angeles Rams | 52 |
| Cleveland Browns at Carolina Panthers | 41.5 |
| New England Patriots at Miami Dolphins | 46.5 |
| Philadelphia Eagles at Detroit Lions | 48.5 |
| Baltimore Ravens at New York Jets | 44.5 |
| San Francisco 49ers at Chicago Bears | 41 |
| Indianapolis Colts at Houston Texans | 46.5 |
| Jacksonville Jaguars at Washington Commanders | 44 |
| New Orleans Saints at Atlanta Falcons | 42.5 |
| Pittsburgh Steelers at Cincinnati Bengals | 44.5 |
| Kansas City Chiefs at Arizona Cardinals | 53.5 |
| Green Bay Packers at Minnesota Vikings | 46.5 |
| Las Vegas Raiders at Los Angeles Chargers | 52 |
| New York Giants at Tennessee Titans | 43.5 |
| Tampa Bay Buccaneers at Dallas Cowboys | 51 |
| Denver Broncos at Seattle Seahawks | 44 |
NFL best bets for Week 1
Saints (-5.5) at Falcons
The Saints are one of the 10 road favorites in Week 1 as they open the regular season against NFC South rival Atlanta. New Orleans split the two-game season series last season, but that was without starting QB Jameis Winston and star WR Michael Thomas, who were both injured. The Saints will have both on the field Sunday as they face an Atlanta defense that will not have standout linebacker Deion Jones (shoulder). The Saints are 4-1 against the spread in their past five games against the Falcons and 14-3 straight up in their past 17 games against teams from the NFC South. We should see the Saints impose their will on both sides of the ball, as they have the advantage in the trenches.
Jaguars (+118) at Commanders
As we know with Week 1, there are always a few upsets that catch us off guard. Last season, we saw underdogs Texans, Bengals, Saints, Dolphins, and Eagles all win in Week 1. We should expect to see the same thing happen on Sunday. The Jaguars are in a prime position to pull off the upset as three-point underdogs to the Commanders.
Jacksonville has a new coach in Doug Pederson, who is a better NFL head coach than Urban Meyer and will have second-year quarterback Trevor Lawrence playing better football this season. Pederson also knows the other quarterback in this Week 1 contest, Carson Wentz. Wentz is the new Commanders' quarterback after only spending one season in Indianapolis. Wentz has a nice set of weapons around him, but he did not have the best luck against the Jaguars last season. Wentz and the Colts lost to Jacksonville 26-11 in a must-win spot in Week 18. Commanders head coach Ron Rivera will have his squad ready, as he's 10-1 against the AFC South over his career. However, do not be surprised if the Jags sneak out with a Week 1 win thanks to their defense and running game. At the very least, we like the plus-money bet.
Chiefs at Cardinals (+6)
For our last best bet, we are going to put hope in the Cardinals and head coach Kliff Kingsbury, who will look to make some noise in their home opener against the Chiefs. On Monday morning, the Chiefs were 4.5-point favorites, but now that has ballooned to six points. That's too many points for a Chiefs' defense that does not have Tyrann Mathieu anymore and an offense looking to replace star wide receiver Tyreek Hill.
Granted, the Cardinals will be without DeAndre Hopkins for the first six games (suspension), but Kyler Murray still has James Conner, Marquise Brown, A.J. Green, Rondale Moore, and Zach Ertz. Last season, the Cardinals were 3-0 ATS and won those three games outright when they were listed as the underdog by five or more points. It remains to be seen with Moore (undisclosed) and Ertz (calf) play; however, if they do suit up. the Cardinals should be able to keep it close in what will likely be a high-scoring game.