Indianapolis Colts vs Arizona Cardinals Picks and Predictions October 12th 2025

Indianapolis Colts vs Arizona Cardinals October 12th 2025

The Arizona Cardinals will visit the Indianapolis Colts in Week 6 of the 2025 NFL season. The game will take place at Lucas Oil Stadium, which features a retractable roof. Fans can catch the action on FOX at 1:00 PM on Sunday, October 12, 2025.

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The Cardinals come into this game with a 2-3 record. They have struggled in their division with a 0-2 record. On the other hand, the Colts have a strong start with a 4-1 record. They have been successful at home, boasting a 3-0 record at Lucas Oil Stadium.

Cardinals vs Colts Key Information

• Sport: NFL
• Teams: Arizona Cardinals vs. Indianapolis Colts
• Venue: Lucas Oil Stadium, Indianapolis, IN
• Date: Sunday, October 12, 2025
• Betting Odds: Cardinals Moneyline +250, Colts Moneyline -311, Cardinals Spread +6.5 (-109), Colts Spread -6.5 (-112), Total Over 47.5 (-108), Total Under 47.5 (-112)

Colts vs Cardinals – NFL Week 6 Betting Preview

The Indianapolis Colts return home with momentum after a 40-6 demolition of Las Vegas, while the Arizona Cardinals limp into Week 6 uncertain whether Kyler Murray will play.

Daniel Jones is thriving in his new home, and the Colts’ offense has been nearly unstoppable, averaging over 32 points per game. The Cardinals, meanwhile, face injury turmoil and off-field distractions in what’s shaping up as a challenging trip to Indianapolis.

The Colts can win if

Daniel Jones keeps leading efficient, turnover-free football. The 28-year-old quarterback has found new life in Indianapolis, posting a 71.3% completion rate and a 105.1 QB rating — both career bests.

The Colts’ offense has produced 163 points through five games, the most since the Peyton Manning era. Running back Jonathan Taylor has complemented Jones with consistent production, while receivers Josh Downs and Michael Pittman Jr. provide reliable targets across all zones.

Even with kicker Spencer Shrader out for the season, the signing of veteran Michael Badgley keeps special teams stable. If the offensive line protects Jones against Arizona’s front seven and the defense forces Arizona into third-and-long situations, Indianapolis can roll to a third straight win.

The Cardinals can win if

They establish the ground game early and protect whichever quarterback starts — Kyler Murray or Jacoby Brissett. Murray’s foot injury could sideline him, and Brissett, a 10-year veteran, is familiar with Lucas Oil Stadium after starting 30 games for the Colts earlier in his career.

Brissett’s composure and short-pass accuracy would be key against a Colts defense that’s built to pressure the quarterback. Running back James Conner and wideout Marvin Harrison Jr. must carry the offensive load if Murray can’t go.

Defensively, Arizona needs takeaways — something they’ve struggled to create during their current three-game losing streak. A strong effort from Darius Robinson (if active) and the pass rush could tilt the momentum early.

Line Movement and Odds

Opening: Colts -7 / Cardinals +7
Current: Colts -7.5 / Cardinals +7.5
Total: 44.0 points

The spread widened slightly as doubts grew over Murray’s health. Indianapolis is 4-1 ATS this season, while Arizona is just 1-3-1 ATS. The Colts are also 3-0 ATS at home in their last three games.

Stay updated on real-time NFL line changes via the NFL odds and scores page. For book comparisons and bonuses, check Sportsbook Reviews or find top agent software at Pay Per Head Reviews.

Matchup Breakdown

Indianapolis ranks fourth in the NFL in total offense (392.8 yards per game) and third in scoring (32.6 PPG). Jones’ quick decision-making has turned the Colts into one of the league’s most efficient third-down teams.

The Cardinals are middle-of-the-pack offensively (21.8 PPG) but rank 27th in total defense, allowing 378 yards per game. Arizona’s secondary has struggled against play-action, which is a key part of the Colts’ system under Shane Steichen.

To dive deeper into team trends and statistical matchups, explore the NFL team stats page and the Expert Betting Guide.

Injury Report

Indianapolis Colts

• CB Kenny Moore II (Achilles) – out
• OG Quenton Nelson (ankle) – questionable
• K Spencer Shrader (knee) – IR
• LB Zaire Franklin (shoulder) – probable

Arizona Cardinals

• QB Kyler Murray (foot) – questionable
• DL Darius Robinson (pectoral) – doubtful
• RB Emari Demercado (disciplinary) – active
• WR Michael Wilson (hamstring) – questionable

Weather in Indianapolis: Dome (roof closed).

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Best Bets and Prediction

With Daniel Jones operating at peak efficiency and the Colts offense humming, it’s difficult to back Arizona — especially with Murray uncertain and internal tension surrounding coach Jonathan Gannon.

The Colts should control time of possession and capitalize on short fields. If Murray sits, expect the line to move closer to -9.

Prediction: Colts 30, Cardinals 17
Best Bet: Colts -7.5 (-110)
Secondary Lean: Over 44 (-110)

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