Dallas Cowboys vs San Francisco 49ers: NFL Predictions, Odds & Picks | Week 10

Sunday, November 15, 2026 · 4:25 PM ET · AT&T Stadium, Arlington, TX · FOX

Odds courtesy of Bet365, correct at time of writing and subject to change.

Dallas is 4-5, hosting a San Francisco team that is 7-1, tied for the best record in the NFL with the Buffalo Bills. I'm leaning toward the 49ers in this one, largely because of the Cowboys’ defence, which has had issues all season.. That gap drives the Cowboys vs 49ers NFL picks for this week.

San Francisco 49ers -4.0: -108

My call is San Francisco -4 at Sports Interaction. San Francisco's defence has allowed just 19.5 ppg this season, well under Dallas's 26.2 allowed, and that gap is the matchup edge driving this pick. Dallas's receiver and cornerback corps are both banged up heading into Sunday, thinning out the group tasked with slowing a 49ers offence that leads the league in total touchdowns. San Francisco's only loss this season was a road loss to Atlanta and while they are on the road again they will win and cover in this game.

Odds from Bet365 and Sports Interaction, correct at time of writing and subject to change.

The Dallas side

Dallas enters off a 27-23 road win over Indianapolis, which was not that impressive facing a reeling Colts team that has lost five in a row. Dak Prescott has led a solid passing offence but second leading receiver George Pickens is questionable. The run game has been better in the last few games but still only ranks 21st in rushing yards per game. America’s Team has a tall task facing a balanced 49ers’ team that ranks third in the league in scoring and sixth in scoring defence. 

The San Francisco side

San Francisco enters off a 38-17 win over Las Vegas, with them getting over their first loss in the previous game. Brock Purdy, Christian McCaffrey, and George Kittle lead a solid offense and a defence that is getting healthier by the week even though they still have some injuries in the secondary. San Francisco is averaging 29.4 ppg, and with a depth of weapons and a shaky Dallas defence, the 49ers will get it done in the Big D winning and covering the spread.

Bet365	Sports Interaction
49ers -4.5	49ers Moneyline
-102	-210
Bet Safety Net Up To C$1,000 or Bet C$10 and Get C$50 in Bonus Bets	125% Welcome Bonus Up To C$750
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Bet365 and Sports Interaction odds, correct at time of writing and subject to change.

San Francisco's -210 moneyline on Sports Interaction works out to a de-vigged win probability of 65% for the 49ers against 35% for Dallas. My own number lands close to that, around 66%, so this looks like an efficient market rather than a line with hidden value. The Cowboys have Prescott and a good passing game but other issues while San Fran is a much more balanced team, which is why they are the pick. 

I'm backing a 30-17 final. San Francisco sits atop the NFC West while Dallas is second in an NFC East where only the Giants own a winning record. AT&T Stadium's dome takes weather out of the equation, so this comes down to roster rather than conditions, and San Francisco has the edge there on both sides of the ball. A 13-point margin clears San Francisco's -4.5 on Bet365, and the combined 47 points stay comfortably under the 55.5 total.