NFL Parlays & Picks: Best Bets for Week 6 (2025)

NFL Week 5 saw a lot of contenders and betting favorites lose outright, demonstrating parity across the league. The Philadelphia Eagles and Buffalo Bills both suffered their first losses of the season, while the Tennessee Titans finally found the win column with an improbable comeback on the road against the Arizona Cardinals.

We’re still hunting for a two-leg early week NFL parlay to win. There have been a lot of bad beats so far, including under 41.5 losing on the Titans’ walk-off field goal attempt. My NFL Parlays & Picks: Best Bets for Week 5 moneyline favorites parlay featuring the Rams and Eagles had both legs lose, while the lone winner was Tampa Bay +3.5. Unfortunately, that was parlayed with under 41.5 total points in the Titans and Cardinals game.

Here are two new NFL parlays to tail, or fade, as we look ahead to Week 6. Follow me on X at Matt_MacKay_ for more NFL betting analysis and free picks.

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NFL Early Week Parlays: Week 6

(Odds courtesy of FanDuel Sportsbook)

Parlay 1 (+253)

Leg 1: Cleveland Browns vs. Pittsburgh Steelers – Under 38.5 (-112)

Division rivalries, especially in the AFC North, tend to be won with stout defense. Cleveland, despite their one-win record, has one of the league’s top defenses, led by edge rusher Myles Garrett.

T.J. Watt and the Pittsburgh Steelers defense have played well in back-to-back wins over the Patriots and Vikings. Now, they’ll host a Browns offense led by rookie QB Dillon Gabriel.

38.5 is a low point total. Yet, the Browns have gone under this number in three out of five games played in 2025. Pittsburgh’s offense, led by QB Aaron Rodgers, has scored 24 or fewer points in three consecutive games.

Let’s bet on defense to reign supreme in this game. It features two of the league’s top defensive ends, plus an inexperienced rookie quarterback on a struggling offense.

Leg 2: New England Patriots vs. New Orleans Saints – Over 45.5 (-115)

We’re laying a total parlay and betting over 45.5 total points between New England and New Orleans in Week 6. The Saints finally claimed their first win of the season with a dominant effort over the New York Giants at home. Now, QB Spencer Rattler and the offense under head coach Kellen Moore will look to go on a winning streak against the red-hot Patriots.

New England just beat Buffalo 23-20 outright on the road on Sunday Night Football. Second-year QB Drake Maye has been solid in the pocket, building a rapport with WR Stefon Diggs and TE Hunter Henry. They’ll face a Saints defense allowing the eighth-most points this season, including the third-most passing touchdowns.

Rattler and the rest of the Saints’ passing attack won’t back down against the Patriots. New England ranks bottom-12 in passing touchdowns (9) allowed, while surrendering 5.7 yards per play, ranked sixth-most in the NFL.

Bottom line here is that points will be scored in bunches. Especially playing indoors in comfortable conditions on a fast track like Caesars Superdome. Bet over 45.5 total points as the second leg in this NFL early week totals parlay.

Parlay 2 (+165)

The Indianapolis Colts’ success may be the biggest surprise of the 2025 NFL season. Led by QB Daniel Jones, Indianapolis just routed Las Vegas, 40-6, with RB Jonathan Taylor racking up three touchdowns. If not for a few miscues against the Rams in Week 5, the Colts would be 5-0 heading into a Week 6 home matchup against the Arizona Cardinals.

The narrative couldn’t be any different with the Cardinals. They blew a 21-6 lead with a negative momentum-shifting play by RB Emari Demercado, leading to their third loss of the season. Arizona also nearly lost to the Saints and Panthers. The Cardinals are simply not a good football team.

Now, Kyler Murray will attempt to lead a stale offense missing its top running back on the road against a Colts offense ranked second in the league under head coach Shane Steichen. We’re going to play it conservatively as a moneyline leg, although -5.5 is also tempting to lay with Indianapolis as a sizable home favorite.

Leg 2: Seattle Seahawks Moneyline (-112)

At the time of this writing, we haven’t seen the outcome between Kansas City and Jacksonville. There’s no doubt that the Jaguars are much improved under first-year head coach Liam Coen, who unlocked their rushing attack with RB Travis Etienne.

Seattle’s 3-2 record has been impressive under QB Sam Darnold. The Seahawks have lost by a combined seven points against a healthier 49ers roster in Week 1 and on a walk-off field goal against a one-loss Tampa Bay team.

Oddsmakers have set the moneyline essentially as a pick’em between the Seahawks and Jaguars. It’s being played in Jacksonville, however, the Seahawks are undefeated on the road in 2025, beating the Steelers and Cardinals.

Seattle is effective at shutting down the run, which will force Jacksonville QB Trevor Lawrence into a more pass-centric role. This will lead to turnovers and the Seahawks offense will capitalize against a fairly porous Jaguars secondary.

Bet Seattle to win outright on the road against Jacksonville to close out this two-leg moneyline parlay in Week 6.