Kansas City Chiefs vs Los Angeles Chargers Prediction, Odds and Picks for Friday, 09/05/25

The Super Bowl losers last season, the Chiefs, hardly seem like a program that’s ready to throw in the towel. Reports from camp indicate that Patrick Mahomes is ready for revenge, performing at an even higher level (is that possible?) leading into this season. Of course, this is only coming from biased sources, like local Kansas City beat reporters and the Chiefs’ coaching staff, but we tend to believe in the hype. Mahomes is a 3-time Super Bowl MVP and an incomparable quarterback, still the measuring stick in the current NFL product. Until he shows any signs of regression, we can count on the best version of Mahomes in Brazil. 

But the Chiefs are more than just Mahomes. They’ll be without Rashee Rice for the first 6 weeks of the season, and they lost veteran left guard Joe Thuney in the offseason, a major part of their pass protection. We have concerns about their offensive line, but we also trust that Kansas City will develop first-round draft pick Josh Simmons and build around veteran center Creed Humphrey. Kansas City also gets back a healthy Isiah Pacheco, All-Pro Travis Kelce, and they have bona fide playmakers in Xavier Worthy and Hollywood Brown. They’re largely the same defense, too, with some added depth pieces. And it’s the same unit that held the franchise on their backs when the offense fluttered last season. 

The Chargers might be the most unchanged team in the NFL entering 2025. Their biggest acquisitions were running back and first round draft pick Omarian Hampton, who will play alongside a banged-up Najee Harris (also an addition), and former Eagles right guard Mekhi Becton. Otherwise, this is a very similar roster and we expect similar results. The Chargers went from good to above average last season with a playoff berth, only to collapse in the Wild Card. Either way, a team led by Jim Harbaugh is a team to respect, particularly in year 2. 

The Bolts played Kansas City hard last season, just 7 and 2-point losses. Both were low-scoring, defensive games, but we expect to see some magic from a vengeful Mahomes on Thursday. Justin Herbert and the Chargers’ offense has upside, but they haven’t been exceptional in any regard yet (13th in points, 20th in yards per game last season). We’ll go with the reigning AFC champions to make a statement since they hold a clear edge on offense and, exponentially more important, the best football player on Earth.

Chiefs vs Chargers prediction: Chiefs -3 (-115) available at time of publishing. Playable at that number.

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Although we expect to see a prime version of Mahomes, it doesn’t mean the Chiefs will be prolific right away on Friday. We trust that the Chargers will bring the same ferocious defense that ranked 2nd in opponent points per game and red-zone success, marks they exhibited in their 2 games against their rival last year. Although they lost both meetings, the Chargers held the Chiefs to just 36 total points and just 2-5 from the red zone. Andy Reid is a master at game-planning offense, but we could say the same about Harbaugh’s defensive wits. This will be a cat-and-mouse minigame throughout the contest, and we expect the Bolts to win plenty of those battles. 

On the other side, the Chargers struggled mightily against KC’s defense last year. Guru Steve Spagnuolo returns to lead a Chiefs’ D that was top-10 in yards and points allowed, although we could argue they peaked against Los Angeles. In their first battle of 2024, Spagnuolo’s group held the Chargers’ offense to a pedestrian 224 total yards and just 4-13 on third downs. The Chargers didn’t improve much in the rematch, either (298 total yards, 6-13 on third downs). A rookie running back and a lot to prove beckons mediocre probabilities that they’ll come close to 20 points on Friday. 

Finally, travelling to Brazil can only complicate matters for each offense as they embark on their first meaningful game of the season, and Sao Paulo will be extremely humid (90-100% forecasted), which can gas out playmakers. This rivalry has been physical and low-scoring historically, a pattern we expect to continue.

Chiefs vs Chargers best bet: Under 45.5 (-110) available at time of publishing. Playable to 44.5.

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