Colts vs. Chiefs Prediction, Odds, Spread, Injuries, Trends for NFL Week 2

Patrick Mahomes and the Kansas City Chiefs put together a statement win in Week 1 of the NFL season, blowing out the Denver Broncos on Monday Night Football.

Mahomes only threw for 184 yards in the win, but he had three total touchdowns (two passing, one rushing) and running back Kenneth Walker III got off to an insane start with his new team. Walker scored twice and ran for 173 yards against a defense that was No. 1 in the NFL in success rate in 2025.

Now, the Chiefs have another primetime showdown in Week 2, as they’ll take on the Indianapolis Colts and Daniel Jones on Sunday night. Jones is coming off an Achilles injury and didn’t get in a groove in Week 1 in a loss to Baltimore.

Oddsmakers have set the Chiefs as 6.5-point favorites at home, where they went 5-3-1 against the spread last season despite winning just six total games.

Indy is facing an uphill battle to make the playoffs in a loaded AFC, especially with the Jacksonville Jaguars and Houston Texans in their division. Last season, Kansas City needed overtime to knock off the Colts, 23-20, so it’s looking for a much easier game in Week 2.

Here’s a breakdown of the odds, a player to watch, betting trends, injuries and much more this Sunday night showdown.

Colts vs. Chiefs Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

Colts +6.5 (+100)
Chiefs -6.5 (-120)

Moneyline

Colts: +245
Chiefs: -305

Total

47.5 (Over -110/Under -110)

Colts vs. Chiefs How to Watch

Date: Sunday, Sept. 20
Time: 8:20 p.m. EST
Venue: Arrowhead Stadium
How to Watch (TV): NBC
Colts record: 0-1
Chiefs record: 1-0

Colts vs. Chiefs Injury Reports

Colts Injury Report

Sean McKeon – questionable
Alec Pierce – questionable
Austin Ajiake – questionable

Chiefs Injury Report

Josh Simmons – questionable
Mansoor Delane – questionable
Cooper McDonald – questionable
Chamarri Conner – questionable

Colts vs. Chiefs Betting Trends

The Chiefs are 1-0 against the spread this season.
The Colts are 0-1 against the spread this season.
The UNDER hit in Kansas City’s Week 1 vs. Denver.
The OVER hit in the Colts’ Week 1 loss against Baltimore.
The Colts were 4-3-1 against the spread on the road in 2025.
The Chiefs were 5-3-1 against the spread at home in 2025.

Colts vs. Chiefs Key Player to Watch

Kenneth Walker III, Running Back, Kansas City Chiefs

The reigning Super Bowl MVP, Walker showed why the Chiefs invested so heavily in him in free agency this past offseason.

The former second-round pick had 23 carries for 173 yards and a score against Denver, adding three receptions for 18 yards and another touchdown through the air. Walker was the bell cow for Kansas City in a blowout win playing 68.1 percent of the offensive snaps and handling the ball in 26 of the 47 plays that he was on the field.

I love this matchup for Walker in Week 2, as the Ravens ran all over the Colts in Week 1. Derrick Henry finished the day with 24 carries for 144 yards and three scores, so Walker should be featured once again on Sunday night.

Colts vs. Chiefs Prediction and Pick

Are the Chiefs back?

Kansas City was a lock to make the AFC title game for several years with Mahomes in his prime, and the star quarterback looked pretty good for his first game back from a torn ACL in Week 1.

He ended up completing 12 of his last 14 passes against Denver, and he has a much easier matchup against a Colts defense that was torched for 41 points in Week 1, ranking 29th in the NFL in EPA/Play.

The addition of Walker has completely changed the dynamic of this Kansas City offense, and we already saw Lamar Jackson and Henry combine for four scores on the ground against Indy in Week 1.

I didn't come into the season high on the Colts, as quarterbacks have struggled recently coming off a torn Achilles. Jones already wasn’t an elite passer, and if he can’t use his legs as much, he’s going to be much easier to slow down.

The Chiefs dominated defensively against Denver in Week 1, posting the No. 1 EPA/Play and the No. 2 success rate in the league.

There’s a real chance that this line moves to Chiefs -7 by the end of the week (it’s already heavily juiced to Kansas City), so I’ll jump on this number while I can.

Pick: Chiefs -6.5 (-120 at DraftKings)

Odds refresh periodically and are subject to change.

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