NFL Week 6 betting: Expert backs Bills in money line favorites parlay while locking 49ers in underdog parlay

The last remaining undefeated teams in the NFL fell in Week 5, with the Denver Broncos beating the Philadelphia Eagles and the New England Patriots stunning the Buffalo Bills. Will the surprises continue in Week 6? Sports fans interested in NFL betting can take advantage of the unpredictable nature of the season to get higher payouts with parlay betting.

Those looking to build parlays for Week 6 NFL games should see what SportsLine expert Jeff Hochman has put together. He's going with two parlays for Week 6, with one featuring only favorites on the money line and the other featuring only underdogs.

Week 6 NFL money line favorites parlay

Betting heavy favorites can be a solid strategy if you want to bet on a three-team NFL money line parlay. This approach focuses on teams with odds of -150 or better, which means you lean towards high-probability outcomes. By pairing three teams that usually have odds between -150 and -350 or even higher, you're not only aiming for consistent, modest returns, but you're also stacking the deck in your favor for a higher chance of winning. Remember that you can still parlay a favorite with odds of -140 or less to avoid laying 2.5 points, which can significantly impact your chances of winning. Remember, you have to win all three legs for a successful wager.

According to BetMGM data, NFL moneyline favorites at -115 or shorter posted a 68% win percentage in 2023, with a 66.5% rate in 2022. Over the six-season period from 2018-2024, NFL moneyline favorites maintained a 66.6% win rate (1,013-508-7). The strength of favorites correlates directly with their odds. In sports betting, if you see teams with odds between -150 and -200, they generally have a solid chance of winning, with around a 60-65% success rate. Teams that are even bigger favorites, with odds from -250 to -400, tend to be more reliable, showing win rates of about 70% to 80%. The 2024 NFL season stood out for favorites, with an overall win rate hitting 71.8%.

NFL favorites dominated the opening week, winning 13 of 16 games for an 81.2% success rate. The second week saw more competitive results, with favorites winning 9 of 16 games for a 56.2% success rate. In Week 3 of the 2025 NFL season, 12 out of 16 favorites won outright, giving betting favorites a 75.0% success rate. In Week 4, favorites struggled on a relative basis, going 10-5-1. Last week, NFL betting favorites had its worst week this season going 8-5.

NFL betting favorites have won 52 out of 77 games through the first five weeks of the 2025 season, resulting in an overall success rate of 67.5%. That number is currently below the 71.8% mark from last year. That percentage has been falling over the last three weeks. What does it mean for Week 6? Will favorites bounce back?

New England Patriots over New Orleans Saints

I was impressed with Drake Maye and some of the throws he made, especially out of the pocket. New England has found its franchise quarterback for the next decade. Maye's historic Week 5 performance against Buffalo saw him complete 22-of-30 passes for 273 yards with zero turnovers while leading a game-winning drive in primetime. His 101.1 passer rating against the league's MVP quarterback demonstrates the poise and capability that will overwhelm New Orleans' struggling secondary, which ranks 28th in opponent passer rating.

New England's dramatically improved offensive line provides the foundation for its resurgence. After investing heavily in retooling the unit, the Patriots now rank 11th in pass protection, according to Pro Football Focus. The Patriots have shown their capacity to contain potent offenses. Against a Saints offense that has scored only 92 points through five games (18.4 points per game), the Patriots' defense should have little trouble limiting New Orleans' scoring chances.

The Patriots possess several specific advantages that should prove decisive. Stefon Diggs has emerged as a consistent deep threat, recording back-to-back 100-yard receiving games for the first time since Julian Edelman in 2019. New England has won their last 13 October games as road favorites, suggesting historical trends favor New England in this exact scenario. Mike Vrabel has this team playing with a lot of confidence, and I don't see them losing this game.

Buffalo Bills over Atlanta Falcons

This game is fascinating in the first of two matchups on Monday Night Football. Buffalo enters off a shocking 23-20 loss to New England as 8-point favorites, creating potential motivation for a bounce-back performance. Atlanta returns from a Week 5 bye, gaining extra preparation time and allowing players to recuperate from nagging injuries. Buffalo has significant advantages in quarterback play, offensive efficiency, and trench performance. The Falcons have lost two of their last three games with two weeks to prepare. In some cases, rest equals rust.

Josh Allen's ceiling and dual-threat profile create far more ways for Buffalo to gain first downs and put points on the board than the Falcons offense can match across four quarters. Allen acknowledged a disappointing loss last week, and Buffalo's passing offense continues to be the most reliable aspect of their game in this matchup. Additionally, Allen and the Bills are 14-4 straight up after a loss since 2021.

Buffalo wins the head-to-head special teams battle in the most critical areas—successful kicking, punt efficiency, and coverage—earning an ST rating that trails only one team. Atlanta gains ST value from turnovers, but does not offset Buffalo's reliability in kicking and field-position control. The Bills' special teams advantage further tilts this Week 6 matchup in their favor.

Pittsburgh Steelers over Cleveland Browns

This might be the best straight-up spot of the year so far, even though these teams have faced each other twice a year for decades. Pittsburgh returns fresh after a Week 5 bye, allowing additional preparation time, complete healing of nagging injuries and precise game-planning. Since 2015, NFL teams coming off a bye have gone 54–27 straight up. This extra week of practice often leads to sharper play in all three areas (offense, defense, special teams), particularly with head coaches who know how to motivate their teams.

This is the Browns' third consecutive road game. Last week, they played in London, facing a 24-hour flight, disrupted routines and circadian stress. Studies of NFL teams traveling across multiple time zones show a measurable drop in defensive efficiency—nearly one extra point allowed per quarter in the first half. Cleveland's secondary is ranked 26th in opponent passer rating (104.5) and could struggle to maintain coverage intensity against a Steelers offense that thrives on quick reads and mismatches.

We have a total of only 38 points, which means scoring could be hard to come by, even with the home team's advantages. I plan to take a chance and bet on the Steelers to win outright, but I am leaning towards the Browns (+6 or higher) for the point spread. It would be wonderful to thread the needle and win both bets.

Week 6 NFL money line underdogs parlay

A very popular option is available if you're willing to take on a bit more risk for a potentially higher reward. Underdog money line parlays offer the largest possible payouts in the NFL betting landscape. Combining three underdogs with odds like +200, +150, and +300 could result in payouts exceeding 20-to-1 or higher. The best part is that, due to the high payouts, underdog parlays can still be profitable even when winning only a small percentage of bets. For example, hitting just one of several large underdog parlays could offset multiple losses and generate overall profit. NFL underdogs have historically outperformed expectations in specific situations, with home underdogs of +2 to +3 winning outright 46-48% of the time.

Carolina Panthers over Dallas Cowboys

First things first, this line seems way off. I made this game Dallas -0.5, so getting +160 on the money line with the home team represents significant value for return on investment. Both teams have faced a similar strength of schedule through Week 5, so there is no real edge in that data point.

Yes, Dallas has the much better offense, averaging 6.1 yards per play compared to the Panthers' 4.9 yards per play. It's quite a gap, but we are only in Week 6. However, the Cowboys' defense is historically poor, ranking 32nd in multiple categories, including third-down defense (58.2% allowed) and 31st in opponent passer rating (117.2). This neutralizes much of their advantages on offense. Carolina's defense is significantly better, especially in pass defense (ranked 13th) and third-down situations (ranked 13th), which should keep the game competitive with a chance to win at enticing odds.

It might be Rico Dowdle's revenge game. Dowdle posted a career-high 206 rushing yards against Miami. The former Cowboys running back played for five years and will definitely be fired up. He was never this good with Dallas, so maybe the coaching staff deserves some credit in Carolina. I would take a strong look at his anytime touchdown prop at plus money.

The Cowboys have lived off their offensive firepower, but their defense has been so bad that it's neutralized their advantages in close games. With Dallas's secondary consistently giving up explosive plays, quarterback Bryce Young doesn't need to be perfect—just avoid turnovers and let his weapons do the work.

Tennessee Titans over Las Vegas Raiders

Admittedly, we got extremely lucky with the Titans' outright win last week at Arizona. I want to ride that momentum to another upset victory with Cam Ward and company indoors. The Titans are due to play a complete game on both sides of the ball. There is a path to get there against this Raiders squad.

The Raiders' secondary ranks among the league's poorest units in covering both wide receivers (5th-highest adjusted completion rate allowed) and tight ends (6th-highest adjusted completion rate allowed). Calvin Ridley projects for significant volume in a dome environment (59.1% pass rate projected) against a secondary yielding 8.04 adjusted yards-per-target to opponents. Ridley had an impressive game last week, recording five receptions for 131 yards. He is capable of achieving similar statistics in this matchup.

Geno Smith leads the NFL with nine interceptions and remains turnover prone. His QBR of 38.6 ranks 28th in the league. The offense has been hamstrung by the absence of tight end Brock Bowers, limiting Smith's weapons in the red zone. Bowers is not expected to return until at least Week 7. Geno Smith is just 11-20-2 against the spread as a favorite, demonstrating the high variance of outcomes when he's under center. With odds close to 2-1, this is a bet you shouldn't miss.

San Francisco 49ers over Tampa Bay Buccaneers

The current market line of Bucs -3 appears accurate based on the statistical breakdown. The 49ers have better underlying metrics in several key areas, including point differential, defensive performance, and third-down offense and defense. However, the Buccaneers' home-field advantage, superior rushing attack and the 49ers' injury concerns justify the 3-point spread.

I like the spot for the road team. The 49ers have three extra days to rest and recover after playing last Thursday while the Buccaneers travel home from Seattle. As long as the 49ers have Fred Warner at linebacker in the middle of their defense, they are a good bet at plus money.

San Francisco owns a net yardage of +60.2, with an offense averaging 375.8 YPG and a defense allowing 315.6 YPG. In contrast, the Buccaneers have a net yardage of +40.0, with an offense averaging 367.0 YPG and a defense allowing approximately 327.0 YPG. Tampa Bay has won four consecutive games that were decided on the final possession. However, that streak will likely end, even if Brock Purdy doesn't play in this game. Mac Jones is a capable quarterback and should perform well against the Buccaneers, who currently rank 27th in opponent passer rating. We also get the better coaching staff.