The Denver Broncos are coming off a historic back-to-back win in which they overcame a two-game deficit to go up 2-1 before heading west to take on the undefeated San Francisco 49ers. They are underdogs and the 49ers look good to start the season. This one will put Denver to the test.
Since the heat will likely be a big factor in this game, Bo Nix and the offense must do a better job of controlling the clock and sustaining their drives. If they find themselves forcing the defense back after multiple three-and-outs, this game could turn ugly for them quickly.
Denver Broncos vs San Francisco 49ers
Sunday, October 4, 2026 at 2:25 PM Mile High time
Levi’s Stadium in Santa Clara, California
ATS Betting Lines: San Francisco -2.5
Moneyline Winnings: Denver +124 / San Francisco -146
Over/under: 47.5
Note: All odds courtesy of FanDuel Sportsbook.
Collectively, our Mile High Report predicts a narrow Broncos 24-23 road victory over the 49ers. Here’s how we predict the result individually:
This is one of those games where I don’t think the Broncos will be able to catch fire in the end. The combination of heat, poor starts, and an inability to sustain drives will catch Denver napping. They mounted a late drive, but the defense was too tired to rally. It’s okay. Losing on the road to an NFC team is the “best” kind of loss and the Broncos still bounce back to win the next two games. 4-2 in the first six games is always my target. – Tim Lynch
I think it will be a tough matchup for the Broncos, but I have confidence they can get the job done on the road against the 49ers. The Broncos need to play better on offense. This involves starting hot with a heavy fast attack. On top of that, Vance Joseph’s defense will have to find a way to slow down Brock Purdy, Christian McCaffrey, George Kittle, and the rest of the 49ers high-powered offense. The time of possession and the turnover battle will be huge. I think Denver found a way to come away with their third win. – Chris Hart
Lots of reasons why the Broncos shouldn’t win – Niners have tons of weapons, great QB, Christian McCaffrey, Trent Williams AND home field advantage. But they don’t have Bo “I will lead fourth quarter comebacks like af boss and you will like it” Nix. So the Broncos came from behind and stole another one. -Laurie Lattimore-Volkman
The Broncos would lead 14-0 at halftime and 17-0 in the 3rd quarter but then would score 27 unanswered in the final 18 minutes of the game and win 27-17. – Scotty Payne
The future of this Broncos team looks very bright. But this week is a tall order. I think the 49ers having home field advantage really dialed up the difficulty for the Broncos. They also have a coach in Kyle Shanahan who will turn red zone trip plans into touchdowns. – Sadaraine
Nix and Denver have a consistency that gives them an advantage over every team. The belief and confidence that no matter what, the Broncos are in every game. Denver’s offense will start faster on Sunday and will make a concerted effort to run the ball. The defense will limit big plays and keep Purdy and the San Francisco offense out of the end zone. Throw in a few sacks and a turnover on defense, and the Broncos find a way again. – Ian St. Clair
This week is a big test for the Broncos. Can the offense play a complete game? Can the defense shut down a consistent offense? I’m not sure those two things can happen. It should be a good game, and I think Denver passes the test. What they won’t do is win. – Adam Malnati