The Denver Broncos are coming off a historic two-game winning streak in which they overcame two scoring deficits in both games to climb to 2-1 before heading west to face the undefeated San Francisco 49ers. They are underdogs and the 49ers look pretty good to start the season. This one will test Denver.
With the heat likely being a big factor in this game, Bo Nix and the offense need to do a better job of controlling the clock and maintaining their drives. If they find themselves forcing the defense to come back after multiple three-and-outs, then this game could quickly get ugly for them.
Denver Broncos vs. San Francisco 49ers
Sunday, October 4, 2026 at 2:25 p.m. Mile High time
Levi’s Stadium in Santa Clara, California
ATS betting lines: San Francisco -2.5
Moneyline Odds: Denver +124 / San Francisco -146
More/Less: 47.5
Note: All odds courtesy of FanDuel Sportsbook.
Collectively, our Mile High Report team is predicting a close Broncos 24-23 road win against the 49ers. Here’s how we predicted the outcome individually:
This is one of those games where I don’t think the Broncos can catch fire late. A combination of heat, poor starts and an inability to sustain drives will put Denver to sleep. They will mount a late attack, but the defense is too tired to rally. But it’s okay. Losing on the road to an NFC team is the “best” kind of losing and the Broncos will bounce back to win the next two games anyway. 4-2 in the first six games has always been my goal. -Tim Lynch
I think this is going to be a tough game for the Broncos, but I have confidence they can get the job done on the road against the 49ers. The Broncos will have to play a lot better on offense. This includes a hot start with a terrific rushing attack. On top of that, Vance Joseph’s defense will need to find a way to slow down Brock Purdy, Christian McCaffrey, George Kittle and the rest of the 49ers’ high-powered offense. Time of possession and the turnover battle will be huge. I think Denver finds a way to get their third win. -Chris Hart
There are plenty of reasons why the Broncos shouldn’t win – the Niners have plenty of weapons, a good QB, Christian McCaffrey, Trent Williams AND home-field advantage. But they don’t have Bo. “I will run fourth quarter comebacks like a boss and you will love it” Nix. Then the Broncos come from behind and steal another one. -Laurie Lattimore-Volkmann
The Broncos would trail 14-0 at halftime and 17-0 in the 3rd quarter, but then scored 27 unanswered in the final 18 minutes of the game and won 27-17. -Scotty Payne
The future of this Broncos team looks very bright. But this week is a big challenge. I think the 49ers having home field advantage really increases the difficulty for the Broncos. They also have a coach in Kyle Shanahan whose plans will turn red zone trips into touchdowns. -Sadaraine
Nix and Denver have a resilience that gives them an advantage over every team. That belief and confidence that no matter what, the Broncos are there in every game. Denver’s offense will get off to a quicker start on Sunday and make a concerted effort to move the ball. The defense will limit big plays and keep Purdy and the San Francisco offense out of the end zone. Add in a few sacks and turnovers for the defense, and the Broncos find a way once again. – Ian St. Clair
This week is a huge test for the Broncos. Can the offense play a complete game? Can the defense shut down a consistent offense? I’m not sure these two things can happen. This should be a good matchup and I think Denver passes the test. What they won’t do is win. -Adam Malnati
What is your score prediction for the Broncos-49ers game? Let us know in the comments section below.
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