The Denver Broncos are coming off an historic back-to-back comeback wins where they would overcome two score deficits in both games to climb to 2-1 before heading west to take on the undefeated San Francisco 49ers. They are underdogs and the 49ers look pretty good to start the season. This one will put Denver to the test.
With the heat likely being 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 out onto after multiple three-and-out’s then this game could get ugly for them quickly.
Game Overview
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
Over/Under: 47.5
Note: All odds courtesy of FanDuel Sportsbook.
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Collectively, our Mile High Report staff is predicting a narrow Broncos 24-23 victory on the road over the 49ers. Here’s how we predicted the outcome individually:
49ers 27, Broncos 16
This is one of those games where I think the Broncos won’t be able to catch fire late. A combination of the heat, poor starts, and inability to sustain drives will catch Denver sleeping. They will mount a late drive, but the defense is too tired to rally. It’s okay, though. Losing on the road to an NFC team is the “best” kind of loss and the Broncos will bounce-back to win the next two games anyway. 4-2 through the first six games was always my target. – Tim Lynch
Broncos 24, 49ers 20
I think this is going to be a difficult matchup 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 much better on offense. That includes starting off hot with a formidable rushing 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. Time of possession and the turnover battle will be huge. I think Denver finds a way to sneak out their third victory. – Chris Hart
Broncos 27, 49ers 24
There are a lot reasons the Broncos shouldn’t win – Niners have a lot of weapons, a good QB, Christian McCaffrey, Trent Williams AND home field advantage. But they don’t have Bo “I will lead fourth quarter comebacks like a f boss and you will like it” Nix. So Broncos come from behind and steal another one. – Laurie Lattimore-Volkmann
Broncos 27, 49ers 17
Broncos will trail 14-0 at halftime and 17-0 in the 3rd quarter but then they will score 27 unanswered all in the final 18 minutes of the game and win 27-17. – Scotty Payne
49ers 34, Broncos 24
The future of this Broncos team looks very bright. But this week is a very tall order. I think the 49ers having home field advantage really dials up the difficulty for the Broncos. They also have a coach in Kyle Shanahan who’s schemes will turn red zone trips into touchdowns. – Sadaraine
Broncos 27, 49ers 23
Nix and Denver have a resiliency that gives them an edge over every team. That belief and confidence that no matter what, the Broncos are in every game. The Denver offense will start faster on Sunday and it will make a concerted effort to run the ball. The defense will limit the big plays and keep Purdy and the San Francisco offense out of the end zone. Throw in a couple of sacks and turnovers for the defense, and the Broncos find a way yet again. – Ian St. Clair
49ers 31, Broncos 27
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 both of those 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
