49ers vs. Cowboys Score Prediction for NFL Week 10 (Expect High-Scoring Affair in Dallas)

By far the best game of Sunday’s 4 p.m. EST window is the rivalry matchup between the San Francisco 49ers and the Dallas Cowboys.

Brock Purdy and the 49ers have weathered a ton of injuries in the 2026 season to get off to a 7-1 start, and they are the favorite to win the Super Bowl through nine weeks. San Francisco has the No. 1 offense (in EPA/Play) in the NFL, and it added Keenan Allen at the trade deadline to bolster a banged-up receiver room.

Dallas isn’t in a playoff spot through the first nine games of the season, sitting at 4-5 with some confounding losses. The Cowboys’ defense is one of the worst in the league yet again, and there is only so much Dak Prescott, CeeDee Lamb and Co. can do to win games.

After picking up a win over Indianapolis in Week 9, Dallas is looking to keep the momentum going at home, where it is a 4.5-point underdog against the No. 1 seed in the NFC.

All season long, the SI Betting team is predicting the final score of every NFL game, a fun way to help our readers decide on their spread, moneyline and total bets. Plus, there’s always a chance that we hit an exact score in the process.

Dallas and San Francisco are both in very different spots in the NFC playoff picture, but a win would go a long way for the Cowboys in the NFC East race. Can they pull off the upset? Here’s a look at my score prediction for this marquee matchup on Sunday.

49ers vs. Cowboys Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

49ers -4.5 (-105)
Cowboys +4.5 (-115)

Moneyline

49ers: -205
Cowboys: +170

Total

55.5 (Over -115/Under -105)

This line has held steady, even with the 49ers dealing with a bunch of injuries across the roster. San Francisco opened as a 4.5-point favorite and the line has stayed there. So has the total (55.5), even though San Fran made a deal for veteran receiver Keenan Allen at the deadline. So, oddsmakers aren’t wavering in this game, which is huge for both team’s chances of winning their respective divisions.

49ers vs. Cowboys Score Prediction

Earlier this week, SI Betting’s Iain MacMillan shared his favorite NFL bet for every game in his Road to 272 column. In this matchup, he’s betting on Dallas to cover at home:

I strayed from my Cowboys' betting strategy last week and paid the price. I said early in the season that anytime the Cowboys play, we should bet against them when they're laying points, bet on them when they're underdogs, and bet the OVER when they're playing in a coin flip. If I had stuck to that strategy, I would've won a lot more bets on their games this season.

Let's get back to that strategy now that they're home underdogs to the 49ers. I know that San Francisco is the better team, especially defensively, but their injuries are starting to pile up. They may be without Deebo Samuel and Mike Evans at wide receiver, as well as Deommodore Lenoir and Renardo Green at cornerback. Those injuries could come back to haunt them against the Cowboys.

I'll take the points with Dallas.

This game features the No. 1 (San Fran) and No. 7 (Dallas) teams in the league in EPA/Play on offense, but they’re 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.

Even with all the 49ers’ injuries – which MacMillan pointed out – 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.

This will probably end up as a high-scoring affair, but I believe the 49ers are more than capable of covering the 4.5 points.

Final Score Prediction: 49ers 34, Cowboys 27

Odds refresh periodically and are subject to change.

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