Nine NFL games from 1 PM ET await us on Sunday, September 25, and this AFC duel in Indiana is one of them, so make sure you don’t miss out on the best Chiefs vs. Colts betting pick and odds.

Kansas City is looking to maintain its perfect start when they visit Indianapolis at Lucas Oil Stadium. The Chiefs are -5.5 favorites on BetDSI Sportsbook, while the total is set at 50.5 points. These AFC rivals haven’t met since 2019.

Chiefs came from behind to beat the Chargers

The Kansas City Chiefs survived the first bigger test in a divisional clash against the Los Angeles Chargers at home. The visitors had a 17-7 lead in the third quarter, but the Chiefs switched to a higher gear and celebrated a 27-24 victory in the end. Interestingly, the Chargers were better in both total yards (401-319) and first downs (21-15), but they committed only one turnover, which proved to be quite costly. Jaylen Watson had a 99-yard pick-six off Justin Herbert in the fourth quarter, and that moment broke the tie.

Patrick Mahomes completed 24 of 35 passes for 235 yards and two touchdowns. He connected with Justin Watson and Jerick McKinnon in the end zone, while Clyde Edwards-Helaire was excellent on the ground with 74 yards on eight touches. Travis Kelce led Kansas City’s receivers with 51 yards on five receptions. Chris Jones registered two sacks, while Willie Gay and Nick Bolton combined for 21 tackles.

LB Willie Gay has been handed a four-game suspension violating the league’s personal conduct policy, and he is permitted to return against the 49ers in Week 7. K Harrison Butker (ankle) is also out, while WR Mecole Hardman (ankle) is questionable to feature on Sunday against the Colts.

Colts fired blanks in a loss to the Jaguars

The Indianapolis Colts are the first team in the new NFL season that failed to get on the scoreboard in their 24-0 road loss to the divisional rivals Jacksonville Jaguars. Nothing worked for Indianapolis on offense, they collected 218 yards opposite Jacksonville’s 331 and won just nine first downs, while the Jags had 21. On top of that, the Colts committed three turnovers and didn’t force a single one on the other end.

Matt Ryan completed 16 of 30 passes for 195 yards and three interceptions. Ashton Dulin was Ryan’s preferred target as he threw seven passes to him, five of which Dulin caught for team-high 79 yards. Jonathan Taylor rushed for 54 yards on nine carries. On defense, Bobby Okereke and Zaire Franklin combined for 21 tackles.

LB Shaquille Leonard has sat out the last two games while recovering from back surgery, and will not return to play against the Chiefs on Sunday.


Kansas City:

  • 9-4 ATS in the last 13 games overall
  • 10-2 ATS in the last 12 games in Week 3


  • 0-4 ATS in the last four games overall
  • 0-4 ATS in the last four vs. AFC rivals

Kansas City Chiefs vs. Indianapolis Colts Pick  

The Colts tied with the Texans and then failed to score against the Jaguars, so I believe the Chiefs will not need much of an effort to secure a victory on Sunday. It’s going to be the first home game for Indianapolis, though, and the hosts will be motivated to show their best, but I don’t think they have the slightest chance against Patrick Mahomes and co. Kansas City’s defense is not great but should be good enough to trouble Matt Ryan and his offensive line that allowed seven sacks in the first two games.

Pick: Take the Chiefs at -5.5 (-110)

The Total

Indianapolis fired blanks in Week 2, so after the opening two games, they scored just 20 points in total. I don’t think they will score more than 17 against the Chiefs on Sunday, and that’s only because Kansas City’s D is not as strong as it was in recent years. The Chiefs can score 30+ here; however, I have faith in the Colts’ solid defense to keep the visitors in check for as long as possible and limit them to field goals instead of conceding plenty of touchdowns. Under is 5-1 in the last six H2H meetings; Under is 7-0 in the Colts’ previous seven games overall, while Under is 6-0 in Indianapolis’ last six vs. AFC rivals.

Pick: Go Under 50.5 points (-110)