The regular season is finally here, as the Kansas City Chiefs take on the Los Angeles Chargers in São Paulo, Brazil on Friday night.

The Chiefs have the opportunity to secure a division win right off the bat after going 5-1 in the AFC West last year. The Chargers haven’t beaten Kansas City since September of 2021, but six of their last seven matchups have been decided by just one score. Both teams are entering this game considerably healthy.

With all that in mind, here are our top 5 things to watch for during the Chiefs’ 2025 season-opener.

LT Josh Simmons, LG Kingsley Suamataia vs. Chargers’ front seven

You can bet Chargers coach Jim Harbaugh and defensive coordinator Jesse Minter are going to throw the kitchen sink at Simmons — who is making his NFL debut, and Suamataia — a second-year player who is learning a new position.

Regardless of how high hopes are for Simmons and Suamataia, the Chiefs will have to help them out. Ways they can do that include lining up a tight end on the left side of the offensive line, and leaving a running back in the backfield to help with pass protection.

Los Angeles has a very good defensive front seven, led by future Hall of Fame linebacker Khalil Mack. Fellow LBs Denzel Perryman and Tuli Tuipulotu, as well as defensive tackle Teair Tart, are also high caliber players. If quarterback Patrick Mahomes is under constant duress, K.C.’s offense won’t be able to push the ball downfield or run the ball effectively.

Chiefs’ interior defensive line vs. Chargers’ rushing attack

The Chiefs have arguably the best DT in the league in Chris Jones, but the quality of depth behind him drastically falls off. K.C. brought back Derrick Nnadi a couple of weeks ago, who is already listed as the starter opposite Jones. Behind Nnadi is veteran Jerry Tillery, as well as rookie Omarr Norman-Lott.

That isn’t the most inspiring group of players. The Chargers are a ground-and-pound offense that features running backs Najee Harris — a multi-time 1,000-yard rusher, and Omarion Hampton — who was one of the best RB prospects in the 2025 NFL Draft. Harbaugh and offensive coordinator Greg Roman will run the ball early and often, so the Chiefs’ interior defensive line better be ready for a huge test.

Patrick Mahomes vs. Derwin James

Mahomes will be in a chess matchup against one of the NFL’s best safeties in James all night long. James has never picked off Mahomes in 10 career games against him, but does have 39 tackles, three sacks, and one fumble recovery against the Chiefs.

K.C. has made no bones about wanting to get back to pushing the ball downfield this season. As exciting as that sounds, Mahomes will have to be cautious of James lurking around. Mahomes has thrown for an average of 273 yards per game against the Chargers’ defense throughout his career, with 27 touchdown passes and seven interceptions.

Chiefs’ CB rotation

The Chiefs made a couple of additions at the cornerback position during the offseason in veteran Kristian Fulton and rookie Nohl Williams. That could allow All-Pro Trent McDuffie to play in the slot more often, where he excelled during the first two years of his career.

However, defensive coordinator Steve Spagnuolo likes using safety Chamarri Conner in the slot as well, so it will be interesting to see how it balances out. It is likely that McDuffie bounces back and forth between the slot and out on the boundary.

Fulton missed most of training camp and the first two preseason games as he recovered from offseason knee surgery. However, he played a lot of snaps in K.C.’s preseason finale, and looked sharp. Jaylen Watson is in his fourth season in Spagnuolo’s system, and Williams flashed during camp.

Chiefs’ pass rush vs. Chargers’ offensive line

The Chiefs’ defense has a golden opportunity to capitalize off L.A. being without All-Pro left tackle Rashawn Slater, who is out for the season after tearing his patella tendon during training camp. The Chargers switched Joe Alt from right tackle to LT, and although Alt is a very good player, he’s not quite at Slater’s level.

That also created a hole at RT, which the Chargers have turned to Trey Pipkins III to fill. Pipkins is a decent run blocker, but a below average pass blocker — surrendering six sacks last season. K.C. needs more out of its pass rush in 2025 after ranking 19th in sacks in 2024. We know Chris Jones will do his thing, but he needs help. Defensive ends George Karlaftis, Mike Danna, Charles Omenihu, and Ashton Gillotte will all get their chances.

Kansas City Chiefs News

Kansas City Chiefs QB Patrick Mahomes has opportunity to break multiple NFL records in Week 1 matchup vs. Chargers

Kansas City Chiefs quarterback Patrick Mahomes will have the opportunity to break multiple NFL records in his Week 1 matchup against the Los Angeles Chargers.

Nick Roesch