NFL Week 12 Best Bets (Predictions for Chiefs vs. Colts, Best Total Bet on Sunday)

The SI Betting team breaks down their favorite bets for Week 12 of the 2025 NFL season, including a pick for the Indianapolis Colts vs. Kansas City Chiefs matchup.

The Kansas City Chiefs and quarterback Patrick Mahomes are favored in Week 12. / Ron Chenoy-Imagn Images

Week 12 in the NFL marks the two-thirds point in the 2025 season, and there are a plethora of great matchups to bet on, including an AFC clash between the Kansas City Chiefs and Indianapolis Colts.

Our editors are locked in that matchup for this week's edition of NFL Best Bets, as there are a limited number of games to choose from on Sunday.

Before every team is back in action in Week 13 for Thanksgiving Week, there are a few bye weeks that we need to navigate in the NFL in Week 12.

SI’s Peter Dewey and Iain MacMillan share their favorite bets for Sunday’s games every week, and we’ve had some solid showings in the second half of the 2025 campaign.

Let’s dive into the breakdowns for each of these picks on Sunday, Nov. 23.

NFL Best Bets for Week 12

Odds via DraftKings Sportsbook.

• Kansas City Chiefs -3 (-120) vs. Indianapolis Colts – Peter Dewey
• Kansas City Chiefs-Indianapolis Colts OVER 49.5 -- Iain MacMillan

Kansas City Chiefs -3 (-120) vs. Indianapolis Colts – Peter Dewey

This Week 12 matchup has become a must win for the Kansas City Chiefs, as they are on the outside of the playoff picture at just 5-5 in the 2025 season.

Kansas City is an impressive 4-1 at home, and I think there are a bunch of reasons to bet on the Chiefs against Daniel Jones and the Indianapolis Colts. 

Yes, Indy is coming out of its bye week, but the Colts are just 1-1 against the spread as road dogs and have played some close games (including a loss to Pittsburgh) as of late.

Kansas City, on the other hand, is 3-0 against the spread when favored at home, and it has a defense that may be able to put a lot of pressure on Jones.

The Colts have gotten to 8-2 on the back of Jonathan Taylor, but the Chiefs are allowing just 4.2 yards per carry this season. While Taylor likely will get his, the Chiefs are third in the NFL in points allowed this season.

If their defense keeps this Indy offense in check, I think Patrick Mahomes can make something happen against an Indy defense that ranks in the bottom 10 in the NFL in passing yards allowed. 

I’m not out on the Chiefs being able to make a Super Bowl run, but they need this game to truly stay in the mix. I’ll trust Andy Reid’s group at home to get it done.

Kansas City Chiefs-Indianapolis Colts OVER 49.5 -- Iain MacMillan

We're keeping this bet as straightforward as it gets.

The Chiefs and the Colts have had two of the best offenses so far this season, so let's bet on there being plenty of points when they meet up in Week 12.

The Colts' offense ranks first in DVOA, first in EPA per play, and second in success rate. Meanwhile, the Chiefs' offense ranks third, third, and fourth in those three respective metrics.

Defensively, both teams have been around average in the league, and Colts' defense has regressed in their last few outings. Let's sit back and root for points in this AFC showdown.

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Odds refresh periodically and are subject to change.

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