3 Bold Predictions for Make-or-Break Cardinals-49ers Clash

The Arizona Cardinals and San Francisco 49ers are set to meet for an epic Week 11 clash - and things could get wild.

Arizona Cardinals tight end Trey McBride (85) yells out after making a first-down catch against the Carolina Panthers at State Farm Stadium on Sept 14, 2025. | Joe Rondone/The Republic / USA TODAY NETWORK via Imagn Images

Round two approaches for the Arizona Cardinals and the San Francisco 49ers as they prepare for a pivotal NFC West divisional showdown. The Cardinals remain winless within the division while the 49ers are within reach of their fourth win to stay alive in the division against the surging Los Angeles Rams and Seattle Seahawks.

This game carries a lot of meaning in the division beyond the fact that it's a battle between hated rivals, and it's going to make things exciting.

With a lot more on the line for these teams than many may realize, I think fans are in store for the most exciting game of the season for each team so far.

Let's get crazy and break down three bold predictions that should get the old adrenaline running.

Trey McBride tops 100 yards again, catches 2 touchdowns

The last time Arizona and San Francisco squared off, McBride caught five passes for 43 yards and a score. In that game, Kyler Murray was under center, and Fred Warner was patrolling the middle of the field for the 49ers. Things have changed dramatically since then, and that doesn't even include Jacoby Brissett as the Cardinals’ new quarterback (plus his connection with McBride).

But it's always (not) funny to see how important one play can be to your defense. Warner was injured against the Buccaneers in Week Six, and since then, the Niners’ defense has been pummeled by tight ends. In four games since then, they have allowed 22 total receptions for 227 yards and four touchdowns to tight ends. Before Warner went down, they allowed 29 receptions for 257 yards and three scores in six games. That's pretty dramatic.

Since Brissett took over, McBride has caught 32 passes for 328 yards and five touchdowns. With those two factors in play, it sets up McBride for his best game of the season. McBride is going nuclear against a 49ers defense he already found success against this season. He's topping the century mark for the second straight game, but I'll go crazy and give him two more touchdowns. I won't predict receptions, but I could easily see double digits.

Former teammates Josh Sweat and Bryce Huff combine for 5 sacks

Sweat has been worth every penny the Cardinals gave him this offseason, as he has recorded eight sacks already. Comparatively, the Cardinals as a whole have 18 sacks, giving Sweat nearly half of that production. It was a natural fit for him to rejoin Jonathan Gannon in the desert, as his two best seasons with the Eagles came when Gannon was his defensive coordinator. It should be a shock to no one that he's dominated.

On the other side of things, Huff is on his third team in as many seasons with varying success. He notched 10 sacks in 2023 with the Jets, and a trade to the Eagles felt like another great spot for him to stack success. Unfortunately, he struggled to find the field for multiple reasons and had just 2.5 sacks in 12 games. He got a fresh start with the 49ers, and he's made the most of it so far with four sacks in eight games.

Huff and Sweat may not have gotten much time to get acquainted last year in Philly, but they will both be on full display on Sunday. I expect Sweat to continue his dominance and Huff to have his best game of the season. With neither team boasting great offensive lines, look for these two in particular to tally up sacks. I have them combining for five total sacks, but I won't try to guess how it's split between them.

Both teams turn the ball over in a sloppy game

Brock Purdy should be back for the 49ers after a long absence due to injuries. He didn't look overly great in his two games, however, with four interceptions. Mac Jones has been solid over eight games, but he's thrown six picks of his own. The rest of the team has collectively lost five fumbles, so the Niners’ offense isn't exactly what you'd call steady.

The Cardinals are much more efficient now that Brissett is starting, with just four turnovers in his four starts. Things are set up nicely for Arizona to have another clean game and even take advantage of a turnover-prone San Francisco team.

However, this is a playoff game for the 49ers. At 6-4, they're on the outside looking in at a wildcard spot, but they can't lose any more traction in a highly competitive NFC West. San Francisco needs this win to stay alive in a wide-open NFC, and they will look to sweep Arizona and secure a winning record in division play with their fourth win. That tiebreaker could win them the division down the road, so expect them to play their best.

This game will be back and forth, and I anticipate turnovers will have something to do with that. The Cardinals still have something to play for, too, and they should have their opportunities to force mistakes. Look for a sloppy, sloppy game with lots of highs and lows and no shortage of emotion.