Tom Brady vs. Aaron Rodgers. It doesn’t get much more marquee than that in the 2022 NFL regular season. The latest NFL Week 3 odds predict a close one, with the Bucs at -2.5 on the spread.

Week 3 of the NFL betting season features a rematch of the NFC title game for the 2020 season, and a matchup of perhaps the best to ever throw a football. 

RELATED: NFL Week 3 Picks, Best Bets and Predictions

It’s also a showdown between two of the favorites in the NFC. The Buccaneers (+300) and Packers (+550) are 1-3 at most online sportsbooks to win the NFC Championship (Eagles are typically No. 2). 

Matt Ryan and the Indianapolis Colts get a litmus-test home game vs. Patrick Mahomes and the Kansas City Chiefs, while Kyler Murray and the Arizona Cardinals get Matthew Stafford and the defending Super Bowl champion Los Angeles Rams in their house. The NFL Week 3 lines are out now, so let's take a look.

NFL Week 3 Odds & Point Spreads

Let's take a look at the NFL Week 3 odds, where you can compare spreads, moneylines and Over/Unders for every game. Don't forget to compare all the NFL Week 3 point spreads at your favorite sportsbooks before wagering on the Week 3 action.

Thursday, Sept. 22

Pittsburgh Steelers at Cleveland Browns, 7:15 p.m. ET

Pittsburgh’s defense ranked dead-last in the NFL in rush yards allowed in 2021, yet it held the top run offense, Cleveland, to 10 and 14 points in a season sweep. Its own run game offered a glimpse; Najee Harris gained a season-high 188 yards in one of those wins over the Browns last year. 

Cleveland’s success is predicated by the run game of Nick Chubb and Kareem Hunt. Cleveland was 8-3 when the team finished with a modest 100 yards on the ground and 0-6 when it didn’t. Only once did the Steelers allow under 93 yards rushing and four times under 105. It won't be in time for this matchup, but Ohio sports betting will be live for Browns fans in the state from Jan. 1, 2023.

Sunday, Sept. 25

New Orleans Saints at Carolina Panthers, 1 p.m. ET

The Saints have won nine of the last 11 against the Panthers, holding Carolina to 10 points or less in three of the last four victories. Defense was the key for New Orleans last season, no doubt: The Saints were 7-1 when the opponent scored 20 points or less and 2-8 when it was 21 or more. 

The Panthers will have Christian McCaffrey, hopefully healthy for a full season. Carolina was 4-3 when he played last year (1-9 when he didn’t). But they are 0-2 with him this year.

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Houston Texans at Chicago Bears, 1 p.m. ET

This is one of the ugliest games of the season, never mind just the NFL Week 3 odds board. Davis Mills and Justin Fields are just getting going on their second years after up-and-down rookie campaigns. The bonus for Chicago is a returning defense that ranked No. 6 in yards allowed in 2021. Houston’s ranked 31st.

Mills was a surprise throw-in at QB with Deshaun Watson’s absence, but he threw for 16 TDs and 10 INTs on a talent-starved Houston offense. The Texans spent its four opening draft picks on a starting WR, a guard and two defensive backs. This game will be a litmus test for new-look Houston, who have started the season with a tie against the Colts and a loss to the Broncos. 

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Kansas City Chiefs at Indianapolis Colts, 1 p.m. ET

No more Tyreek Hill for the Chiefs and QB Patrick Mahomes, but history says Mahomes should be fun. Through 63 games, Mahomes ranks 1st or 2nd in yards, TDs and QB rating. The addition of JuJu Smith-Schuster and Marquez Valdes-Scantling should aid Mahomes’ efforts against Indy’s subpar pass D. Kansas sports betting is live for bettors in the state and the latest NFL Week 3 odds have the Chiefs as -7 favorites.

Matt Ryan led the NFL in completions in 2019 and 2020, and won the NFL MVP award six seasons ago. The last time he played alongside a run game that ranked higher than 27th was 2017. He’ll get that with Jonathan Taylor and the No. 2 run game of a season ago. KC ranked bottom 10 vs. both the run and pass last year. 

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Buffalo Bills at Miami Dolphins, 1 p.m. ET

The Bills have won seven straight in this AFC East rivalry and the past three haven’t been close, winning by an average of 26.7 ppg. Over the last six games and three seasons, QB Josh Allen has thrown for 16 TDs and only two INTs. The Bills are the current favorites on NFL futures markets to win Super Bowl 57, priced around +400 at time of publication. They are favorites to win this AFC East clash, too, in NFL Week 3 odds markets.

Miami has ranked 22nd or worse offensively every year since 2015/16, but the team made headway to improve upon that. This could be a good test to see if the Dolphins can keep competing in high-scoring games with WRs Tyreek Hill and Jaylen Waddle and RBs Chase Edmonds and Raheem Mostert new to the mix. They passed their first test in Week 2 vs. the Ravens in style.

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Detroit Lions at Minnesota Vikings, 1 p.m. ET

The Lions were 0-10-1 before shocking the Vikings 29-27 at home in Week 12. It marked the third-highest yards total and his first three-TD game for QB Jared Goff. The Vikings ranked 29th in pass D that year and could be starting two rookies in the defensive backfield. 

The Vikings had won eight consecutive games in this NFC North series until the Lions shocked them last December. They’ve won four in a row at home against the Lions, however, three of them by at least 13 points. The Dalvin Cook-Kirk Cousins tandem should find success against a Lions defense that struggled to stop nearly everyone in 2021 and has struggled through two weeks in 2022. 

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Baltimore Ravens at New England Patriots, 1 p.m. ET

Lamar Jackson’s career trajectory has been going in the wrong direction. Since winning the MVP in 2019, his QBR rating has dipped from 83.0 to 67.3 to 50.7 in 2021. That said, when he didn’t play down the stretch the Ravens lost their final four games to miss the playoffs. 

The Patriots ranked No. 2 last year in pass yards and pass TDs allowed, and the path is open for Mac Jones to have himself a day. No team allowed more pass yards than the Ravens in 2021, though moderation was the key to Mac’s success. New England was 7-1 when he threw for 228 yards or fewer. The NFL Week 3 odds have this game at Ravens -3.

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Cincinnati Bengals at New York Jets, 1 p.m. ET

The Jets ranked dead-last in the NFL in both yards allowed and points allowed, now here comes the Bengals, who scored 32-plus points in four of the final seven weeks after the bye week. Cincy was 7-1 when Joe Mixon managed a modest 65 yards and 3-6 when he didn’t. Cincy had just 41 in the surprising loss last year but the Jets allowed 96-plus in all but two games. The Bengals need this one after opening the season at 0-2.

The Jets were on the skids and the Bengals on their way to a Super Bowl, but New York got a 34-31 win on Halloween last year. Zach Wilson missed that game (Mike White threw for 405 yards) and he might miss this one, too. Joe Flacco led the Jets to a Week 2 victory over the Browns.

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Las Vegas Raiders at Tennessee Titans, 1 p.m. ET

The Raiders’ pass attack should find success against a Titans defense that was 26th vs. the pass and just got gashed by the Bills on Monday Night Football. 

On the other side, Derrick Henry and the Titans may find opportunity against the Raiders, who allowed 114.3 ypg on the ground. But Ryan Tannehill’s success is the team’s success. When he completed 62% of his passes, the Titans were 12-2. They were 7-1 when he didn’t toss an INT. Vegas’ defense allowed 66.3% of passes to be caught.

Philadelphia Eagles at Washington Commanders, 1 p.m. ET

The Eagles took both meetings, in Weeks 14 and 16, part of their late run to clinch a postseason berth. Here they face a Washington D that really struggled vs. the pass. Many believe Philly’s success was predicated by the run, especially that of QB Jalen Hurts. But the team was 5-2 when he rushed eight or fewer times and 3-6 when he was over that number. Philly are 2-0 and look great.

From Washington’s perspective, the story will likely revolve around Carson Wentz against the team that drafted him. Wentz was maligned his one year in Indy but he threw for 27 TDs and seven INTs. Washington managed over 250 pass yards twice last year. The NFL Week 3 odds for this game opened as a Pick Em but they've drifted in favor of the Eagles.

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Jacksonville Jaguars at Los Angeles Chargers, 4:05 p.m. ET

We know the Chargers can score but can the Jaguars keep up? Four of the last five meetings between these teams have totaled at least 52 points. Scoring is what Jacksonville struggled to do last year. Only twice did it manage over 21 points. L.A. allowed 21-plus points in all but four games. 

Justin Herbert is off to a record-setting career through two seasons. The key to success against him is turnovers. The Chargers were unbeaten when he didn’t toss an INT. That could be bad news for the Jaguars, who managed six picks in 17 games last year. This is one of the largest NFL Week 3 lines on the board at Chargers -7. But the health of Justin Herbert (ribs) is in question.

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Los Angeles Rams at Arizona Cardinals, 4:25 p.m. ET

Matthew Stafford threw for 769 yards, eight TDs and one INT in three games vs. Arizona last year. The Rams were especially tough on the road, winning seven of nine in the regular season. The Cards were just 3-5 at home. 

The Cardinals have improved in each of the three seasons with Kyler Murray at QB, including back-to-back playoff berths. Next step: Getting past the defending Super Bowl champion Rams. Murray is only 1-6 vs. the Rams in his career and L.A. has won 10 of 11 in the series. For that reason, the Cards are underdogs according to the latest NFL Week 3 odds.

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Atlanta Falcons at Seattle Seahawks, 4:25 p.m. ET

The Falcons’ defense was a tatters last year but perhaps this is the offense for which to gain momentum. Seattle was 1-2 last year without Russell Wilson, a harbinger of 2022, managing 10 and 20 points against teams not named the Jaguars. The Falcons were 7-2 when allowing 28 or fewer points in 2021. 

Counterpoint: The Falcons allowed 29-plus points in eight out of 17 games and lost them all. Seattle still maintains one of the premier WR duos in Tyler Lockett and DK Metcalf. If Atlanta can allow 281 yards to the Dolphins and 290 to Washington, the Seahawks may have a day of their own here. 

Green Bay Packers at Tampa Bay Buccaneers, 4:25 p.m. ET

The last time Rodgers faced this defense, he threw for 346 yards and three TDs, but Tampa still won. Last season it was clear the team goes through No. 12. The Packers were 13-1 when he passed for over 140 yards. Green Bay ranked top 10 in both total offense and defense, and exactly 10th in points scored and allowed. 

While Green Bay is above average in most instances, the Buccaneers displayed extremes. No team threw for more passing yards and only two allowed fewer rushing yards, but they ranked bottom 10 vs. the pass and in rushing the ball. Rodgers’ four lowest passing totals were on the road. The Bucs were a far better team at home, outscoring opponents by an average of 14.2 ppg compared to 3.2 on the road. They are -2.5 favorites, according to the latest NFL Week 3 odds.

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San Francisco 49ers at Denver Broncos, 8:20 p.m. ET

Perhaps no team was happier when Russell Wilson was traded out of the NFC West, but they face their old rival here. Wilson was a whopping 17-4 against San Francisco during his time in Seattle, with 37 TDs and 10 INTs.

The Broncos went just 7-10 last season, playing in the NFL’s toughest division where they won one game against the Chiefs, Raiders and Chargers combined. But they also went 4-1 against the NFC, with three of those victories by at least 14 points. Jimmy G is back under center in San Fran, while the Russ era in Denver is off to a shaky start.

RELATED: NFL Week 4 Best Bets, Picks and Predictions

Monday, Sept. 26

Dallas Cowboys at New York Giants, 8:15 p.m. ET

Dallas has won nine of 10 in this NFC East rivalry; four of the last five wins were by 15 or more points. RB Ezekiel Elliott has scored at least one TD in five straight vs. the Giants. But, following the Week 1 injury to Dak Prescott, the NFL Week 3 odds have the 2-0 Giants as -2.5 favorites.

This is a huge game for Daniel Jones to prove he can move the Giants up the NFC East pecking order. In 25 games over the last two seasons, Jones has just 21 TDs with 17 INTs. Cooper Rush will be on the other sideline for Dallas. Jones must outplay him and get the W for New York to keep his job long-term.

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Opening Week 3 Odds vs Current Lines

Here's a look at the opening NFL Week 3 point spreads for each game and how the lines have moved ahead of Week 3:

Current NFL Week 3 odds up-to-date as of Sept. 20, 2022 and via DraftKings Sportsbook