Broncos Can’t Afford to Lose These 2 Matchups vs. 49ers.

The San Francisco 49ers have one of the NFL's most explosive offenses and one of the best defenses, which gives the Denver Broncos a tough, unique challenge.

Heading to San Francisco, the Broncos won't have the home-field advantage they've enjoyed the past two weeks, but Levi's Stadium has been the site of big-time success for Denver (Super Bowl 50). All-time, the two teams are 8-8 against each other and 2-2 in their last four meetings.

A key for Denver will be limiting explosive plays on defense and finding them on offense. Given what the 49ers do on both sides of the ball and the quality of their run game, Denver will need to put up multiple touchdowns in the first half.

If the Broncos are unable to score early, the 49ers have the talent and coaches to run away with this game, even with all the injuries they have sustained. Two matchups will be pivotal.

Let's examine them.

Broncos WR Jaylen Waddle vs. 49ers CB Renardo Green

The Broncos' most explosive player is Waddle, and they will need him to get going to not only generate explosives but also create openings for other weapons. Denver needs to match him up with Green, who was terrible in 2025 but had an outstanding start to this season before being picked on last week.

Green has allowed nine of 12 targets to be caught for 88 yards and a touchdown, with seven catches on nine targets for 65 yards and the touchdown coming in San Francisco's Week 3 game. Green can be dangerous and aggressive when going after the ball, with an interception and a pass breakup this season, so Bo Nix will need to be on target when targeting him in coverage, regardless of the receiver.

Waddle has been quiet this season outside of his big Week 2 game against the Jacksonville Jaguars. He has just three catches on 10 targets for 12 yards in the Broncos' two other games.

When Waddle is involved in the offense, the Broncos are clearly more explosive (which is why they brought him in), and the unit runs more smoothly. That's why Waddle vs. Green is a key matchup for this game.

Broncos OLB Nik Bonitto vs. 49ers OT Trent Williams

The best way to prevent explosive plays defensively is through trench play. Denver will need to be stalwart against the run — a tough ask against the 49ers — and generate pressure on Brock Purdy, which also won't be easy.

Fortunately, Denver has one of the NFL's most explosive edge defenders in Bonitto, but he'll face one of the league's best left tackles in Williams.

Williams is an excellent player who excels in both the run game and pass protection. He has allowed only five pressures on 84 pass-blocking snaps, and he shut down Myles Garrett in Week 1.

In the run game, the 49ers have run behind Williams 22 times for 101 yards, two touchdowns, and five first downs.

Bonitto isn't the best run defender, which raises concerns about the 49ers targeting him on the ground. He should at least be able to impact the passing game.

Denver needs Bonitto to make the pocket muddy for Purdy with San Francisco's explosive pass-play rate. Getting by Williams won't be easy, but Bonitto has a track record of showing up well against some really tough tackles.

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