49ers vs. Cardinals score: Jimmy Garoppolo throws four TDs in Mexico City as San Francisco takes NFC West lead

The 49ers' defense also dominated

The Cardinals got a fine performance from Colt McCoy in Week 10, when the backup filled in for an injured Kyler Murray under center. On Monday night, starting at quarterback once more, he hardly had a chance facing DeMeco Ryans' 49ers defense. Looking to win Arizona its second straight game in an effort to creep closer to .500 in the NFC West, he and the Cardinals instead took it on the chin before a roaring Mexico City crowd. San Francisco racked up nine tackles for loss and two turnovers, while Jimmy Garoppolo spread the ball around in one of his best outings of the year, leading Kyle Shanahan's squad to a 38-10 victory to claim the division lead.

Arizona kept things close through halftime, with McCoy feeding DeAndre Hopkins and James Conner capping a second-quarter scoring drive with a touchdown. But the 49ers pulled away early in the second half, getting big gains from Christian McCaffrey, Deebo Samuel and Brandon Aiyuk in a total team win. They move to 6-4 with the decision, dropping Arizona to 4-7.

Here are some additional takeaways from Monday's showdown across the border:

Why the 49ers won

You can start with the defense, which has often been their pillar under Ryans' direction: respected as he may be filling in for Murray, Colt McCoy never stood a chance once the Cardinals fell behind and Nick Bosa and Co. pinned their ears back. San Francisco "only" logged three sacks, but the front four affected Arizona's pocket on the regular, battering the veteran QB until he was replaced by Trace McSorley late. Bosa alone had three QB hits, while Dre Greenlaw, Kevin Givens and Fred Warner each lived in the backfield as well.

Offensively, the 49ers were just as, if not more, impressive. Jimmy Garoppolo has had an underrated year, but he turned in easily his best outing of 2022, even as Kyle Shanahan shied away from a run-heavy approach. Not only did the QB show timely mobility adjusting in the pocket, but he got everyone involved at the right times, enabling McCaffrey (100+ yards), Samuel (90+ yards), Aiyuk (2 TDs) and George Kittle (2 TDs) to have spotlight moments. With quick decisions and accurate passes, they were incredibly efficient even while trailing in time of possession.

Why the Cardinals lost

It starts with Kliff Kingsbury's offense, as has often been the case. While Colt McCoy had the club competitive early, his line did not hold up as the game wore on, and then neither did he. After an early run of Greg Dortch catches thanks to Rondale Moore's latest exit due to injury, the only thing working were throws to Hopkins, who still never managed a breakaway play. James Conner got a decent amount of work but did precious little with it. And a pair of failed fourth-down tries exacerbated the issues, as did five penalties by one of the most undisciplined lineups in the NFL. Defensively, they also eroded, getting almost no pressure on Garoppolo down the stretch and showing half-hearted effort on Kittle's second TD, which all but sealed the defeat.

Turning point

Down just 7-3 in the second, the Cardinals were moving relatively well, threatening their second lead of the night by keeping Hopkins busy on the outside. At midfield, however, they went backward after the star receiver got flagged for taunting following a first-down catch in traffic. Then, two plays later, McCoy had a dump-off bounce off the hands of James Conner and into the diving arms of Jimmie Ward. Sure, Arizona would rebound with a TD drive of its own later in the quarter, but that turnover led to a quick 49ers score and kept momentum in San Francisco's favor for the remainder of the contest.

Play of the game

You might've said Garoppolo's first TD, a bullet to Aiyuk in tight coverage; or his second, to a wide-open Kittle after a step up in the pocket; but Samuel's reverse, which he promptly took past the entire Cardinals defense down the sideline, was a reminder of just how explosive he can be in multiple roles for San Francisco:

What's next

The 49ers (6-4) will return home on Thanksgiving Weekend to host the Saints (4-7), who edged the Rams with a big day from Andy Dalton in Week 11. The Cardinals (4-7), meanwhile, will host the Chargers (5-5), who are fresh off a close loss to the rival Chiefs in prime time.

[Nov 21, 2022 at 11:10 pm ET · Jared Dubin]

Well, Womack got the pick anyway, just not the six.

[Nov 21, 2022 at 11:07 pm ET · Jared Dubin]

That should've been the first career pick-six for Womack, but there's a reason that some guys play DB and not WR.

[Nov 21, 2022 at 11:03 pm ET · Jared Dubin]

What a night for Dortch. But some of that gain will be coming back. 

[Nov 21, 2022 at 11:01 pm ET · Jared Dubin]

Jordan Mason getting some work here at the end of the game. Jimmy G and most of the rest of the starters are on the sideline.

[Nov 21, 2022 at 11:00 pm ET · Jared Dubin]

Cardinals are punting on fourth-and-6 near midfield with 8 minutes left while down by 21 points. At that point, why even play the rest of the game?

[Nov 21, 2022 at 10:58 pm ET · Jared Dubin]

Uh-oh. Dre Greenlaw with some sort of injury here on a drive that basically means nothing. Tried to punch the ball out of McBride's hands and hurt his hand or wrist.

[Nov 21, 2022 at 10:52 pm ET · Jared Dubin]

Nobody even comes close to tackling him there, either.

[Nov 21, 2022 at 10:52 pm ET · Jared Dubin]

George Kittle is the YAC master, folks. 

[Nov 21, 2022 at 10:51 pm ET · Jared Dubin]

Deebo couldn't have been more wide open on that third down. No Cardinals defenders in sight.

[Nov 21, 2022 at 10:46 pm ET · Jared Dubin]

Looked like McCoy had McBride open at the first down market, but tried to fit in a throw to Dortch coming across the field instead. Not sure why he went there with the ball.

[Nov 21, 2022 at 10:45 pm ET · Jared Dubin]

McCoy is really taking a pounding here. Some huge hits from this 49ers front that can just tee off on him now.

[Nov 21, 2022 at 10:44 pm ET · Jared Dubin]

Second Nick Bosa penalty of the night, but the first one that gets accepted. He jumped offside on the big Greg Dortch catch earlier.

[Nov 21, 2022 at 10:36 pm ET · Jared Dubin]

And Aiyuk is in the end zone again. Niners blow this one open.

[Nov 21, 2022 at 10:34 pm ET · Jared Dubin]

McCaffrey comes back in and immediately picks up a first down through the air from the slot, with Deebo lined up in the backfield. Sheesh.

[Nov 21, 2022 at 10:32 pm ET · Jared Dubin]

Mitchell is now up to 52 yards on six carries. Every run has been a chunk gain of some kind. Juszczyk leading the way around the corner right there.

[Nov 21, 2022 at 10:31 pm ET · Jared Dubin]

San Francisco using McCaffrey to establish a lead and then Mitchell to ice games away is actually a pretty good formula, if they can enact it weekly.

[Nov 21, 2022 at 10:28 pm ET · Jared Dubin]

Oh my... Givens just absolutely clobbered McCoy. Totally untouched through the line.

[Nov 21, 2022 at 10:24 pm ET · Jared Dubin]

Marco Wilson had a chance for a big play on that third-and-long after Brandon Aiyuk fell down on the route. But Aiyuk got his hand up as he slipped, which might have distracted Wilson.

[Nov 21, 2022 at 10:22 pm ET · Jared Dubin]

Deebo Samuel looks like he's having cramps on the sideline. He's getting some theragun therapy on his calf at the moment.

[Nov 21, 2022 at 10:18 pm ET · Jared Dubin]

And then he misses Dortch on fourth down. Niners ball, with a chance to make it a three-score game.

[Nov 21, 2022 at 10:18 pm ET · Jared Dubin]

Back-to-back dangerous throws from McCoy, first on a quick out to AJ Green and then down the field to Hopkins. First one was completed, second knocked away.

[Nov 21, 2022 at 10:13 pm ET · Jared Dubin]

Looked like the rookie TE, Trey McBride, ran the wrong route on that second-down play. Cards pick it up with a third-down conversion anyway, Hopkins working on a crosser.

[Nov 21, 2022 at 10:11 pm ET · Jared Dubin]

By far the best run of the night for James Conner. Actually found a crease in the left side of the line.

[Nov 21, 2022 at 10:07 pm ET · Jared Dubin]

We wrote about that play the year the 49ers went to the Super Bowl. They like to have their tight end fake like he is blocking one way, then wheel around and be a lead blocker on the end around.

[Nov 21, 2022 at 10:07 pm ET · Jared Dubin]

Deebo. House call.

[Nov 21, 2022 at 10:06 pm ET · Jared Dubin]

Mitchell immediately ripping off some nice gains again. Just like last week. 

[Nov 21, 2022 at 10:04 pm ET · Jared Dubin]

Jimmy G is just about automatic on QB sneaks. Just got another one right there. He must've learned something from Tom Brady when he was in New England.