NFL Week 10 Best Bets (Predictions for 49ers vs. Cowboys, Texans vs. Browns on Sunday)

Half of the 2026 NFL season is in the books, and there are only nine more regular season weeks left to bet on football with nearly every team (outside of a couple bye weeks) in action.

Week 10 has a ton of great matchups, including the final Sunday morning overseas game with the New England Patriots taking on the Detroit Lions. That's one of several marquee matchups to consider betting on:

Minnesota Vikings vs. Green Bay Packers
Carolina Panthers vs. New Orleans Saints
San Francisco 49ers vs. Dallas Cowboys
Pittsburgh Steelers vs. Cincinnati Bengals (SNF)

Every week throughout the 2026 season, the SI Betting team of Iain MacMillan and Peter Dewey share their NFL Best Bets. The goal of this column is simple:

We choose our favorite bet for Sunday or Monday, and our awesome readers get a chance to ride with us, or fade us. Plus, we'll keep track of our record here to see how we fare throughout the season.

Week 9 was a fairly successful one for the team, as Dewey hit his bet on the Denver Broncos to pick up a win over Carolina while MacMillan's underdog pick for the New York Jets-Kansas City Chiefs game fell short. The Jets were in the game in the first hafl, but they wilted in the second half in a blowout loss.

In Week 10, there are two favorites that our team is targeting for the 14-game slate, as the Broncos, Chicago Bears, Philadelphia Eagles and Tampa Bay Buccaneers are on the bye.

MacMillan has picked every single game in his Road to 272 column (like he does every week), so if we don't hit the game you want to bet on in this story, make sure to check out his column!

Now, let's kick off the second half the season with a couple of road favorites to bet on Sunday!

NFL Best Bets for Week 10

Odds via DraftKings Sportsbook and FanDuel Sportsbook

San Francisco 49ers -3.5 (-110) vs. Dallas Cowboys – Peter Dewey
Houston Texans -4.5 (-115) vs. Cleveland Browns – Iain MacMillan

San Francisco 49ers -3.5 (-110) vs. Dallas Cowboys – Peter Dewey

Sunday’s game between the San Francisco 49ers and Dallas Cowboys has a sky-high total, as it features the No. 1 (San Fran) and No. 7 (Dallas) teams in the league in EPA/Play on offense.

While Dak Prescott and the Cowboys should be able to score with the 49ers, these teams are very different on the defensive side of the ball. Dallas is 31st in the league in EPA/Play and sits in the bottom five in yards per play allowed. That has cost the Cowboys multiple games, including shocking losses to Tampa Bay (with Jalon Daniels at quarterback) and Arizona (with Gardner Minshew replacing Jacoby Brissett) at home.

Even with all the 49ers’ injuries at this point in the season, I keep coming back to one thing:

I don’t trust this Dallas defense.

The Cowboys haven’t been able to stop some of the worst teams in the NFL, including Arizona a couple of weeks ago, and they are taking on a San Fran defense that is No. 9 in the league in EPA/Play and No. 3 in yards per play allowed. So, the 49ers may not be at full strength, but this isn’t going to be a walk in the park for the Cowboys’ offense either.

This line opened with the 49ers as 4.5-point favorites, but it has since come down in favor of Dallas. Even with the Cowboys (4-5) in desperate need of a win to keep pace in the NFC East, San Francisco has shown us all season long that it is one of the best teams in the NFL.

I’ll take the Super Bowl favorite to cover on the road in Week 10.

Houston Texans -4.5 (-115) vs. Cleveland Browns – Iain MacMillan

I’m buying some stock in the Houston Texans. We all know about how good their defense is when they’re in peak form, but now enough people are talking about how good their offense has been this year, something we haven’t seen in a number of years for the Texans.

Heading into Week 10, they rank eighth in the league in EPA per play and since Week 4, C.J. Stroud ranking second amongst all quarterbacks in adjusted EPA per play and sixth in completion percentage over expected.

Now they get to face a Cleveland Browns team that’s not nearly as good as their record indicates, ranking 21st in the league in net yards per play at -0.2. They’re also going back to Deshaun Watson at quarterback, who is a step below Shedeur Sanders. Last week, Sanders almost led the Browns to a big win against the Saints.

I have no problem laying the points on the Texans on Sunday.

Odds refresh periodically and are subject to change.

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