Cardinals vs. Colts Final Score Prediction for NFL Week 6 (Bet on Indy to Win)

The Cardinals are in a dangerous spot following their Week 5 collapse.

Jonathan Taylor and the Indianapolis Colts are favored against the Arizona Cardinals on Sunday. / Trevor Ruszkowski-Imagn Images

The Arizona Cardinals need a break and it doesn’t appear like they’re likely to get one this weekend. They’ll visit the Indianapolis Colts as a seven-point underdog in Week 6 in hopes of ending their three-game losing streak.

The Colts marched to a 4-1 record with a dominant blowout win over the Las Vegas Raiders in Week 5 and are in control of the AFC South. Their offense is chugging along with Daniel Jones under center and they have a real chance to win their division. On paper, Indianapolis appears to be too much for a Cardinals team that’s only beaten the New Orleans Saints and Carolina Panthers this season.

Here’s our score prediction ahead of kickoff.

Cardinals vs. Colts Odds, Spread and Total

Odds via FanDuel Sportsbook

Spread

• Cardinals: +7 (-105)
• Colts: -7(-115)

Moneyline

• Cardinals: +290
• Colts: -360

Total

• 46.5 (Over -115/Under -105)

Arizona has been all over the place this season while Indianapolis has been steady. The Colts are a perfect 3-0 against the spread at home.

Cardinals vs. Colts Final Score Prediction

The Colts’ balance on offense has worked wonders for them in 2025. They rank fourth in total passing yards (1,265) and only four teams are averaging more yards of offense (381.2) per game.

The Cardinals are fielding a bottom-five passing attack and there’s no telling how that will be affected if Kyler Murray isn’t at 100 percent on Sunday. He’s day-to-day with a foot injury that bothered him in Week 5.

Bettors should note that only four defenses have given up more passing yards than Arizona’s in 2025. Jones has all the tools to hand the Cardinals a fourth straight defeat.

Final Score Prediction: Colts 28, Cardinals 20

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Odds refresh periodically and are subject to change.

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