Arizona Cardinals vs Indianapolis Colts Prediction, Preview and Odds - 10/12/2025

Game Time: 1:00 pm ET, Sunday, October 12, 2025

Venue:  Lucas Oil Stadium, Indianapolis, IN

Where to Watch:  FOX

DraftKings:  Point Spread:  Cardinals +6.5, Colts -6.5; Over/Under:  47.5 points

Bet365:  Point Spread:  Cardinals +6.5, Colts -6.5; Over/Under:  47.5 points

BetMGM:  Point Spread:  Cardinals +6.5, Colts -6.5; Over/Under:  47.5 points

Arizona Cardinals:  2-3 (4th place, NFC West)

Indianapolis Colts:  4-1 (1st place, AFC South)

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Arizona Cardinals:  lost their last game at home against the Tennessee Titans 22-21.

Indianapolis Colts:  won their last game at home against the Las Vegas Raiders 40-6.

The Cardinals are entering this game with a 2-3 record overall and they have a 0-2 record in their divisional games too. They are 1-2 in their home games, 1-1 in their road games, and they are also 0-0 in their neutral site games this season, but they will be on the road for this game. They lost their last game against the Tennessee Titans 22-21. Kyler Murray was the starting QB and he completed 23/31 passes for 220 passing yards, 0 touchdowns, and 0 interceptions. Emari Demercado led the team in rushing yards with 81. Marvin Harrison Jr. led the receivers with 98 receiving yards on 4 receptions. Mack Wilson Sr. led the defense in that game with 4 solo tackles and 2 assisted tackles while Josh Sweat led the defense in sacks with 2. Dadrion Taylor-Demerson came away with the only interception for them in that one.

 

 

 

The Colts are entering this game with a 4-1 record overall and they have a 1-0 record in their divisional games too. They are 3-0 in their home games, 1-1 in their road games, and they are also 0-0 in their neutral site games this season, but they will be at home for this game. They won their last game against the Las Vegas Raiders 40-6. Daniel Jones was the starting QB and he completed 20/29 passes for 212 passing yards, 2 touchdowns, and 0 interceptions. Jonathan Taylor led the team in rushing yards with 66 and 3 TDs. Ashton Dulin led the receivers with 55 receiving yards on 2 receptions. Austin Ajiake led the defense in that game with 4 solo tackles and 4 assisted tackles while Samson Ebukam, Zaire Franklin, DeForest Buckner, and Tyquan Lewis each led the defense in sacks with 1. Mekhi Blackmon and Laiatu Latu each came away with 1 interception for them in that one.

The current betting odds have the Colts listed as a 6.5 point favorite in this game according to Draftkings Sportsbook. The Colts have looked great in their games this season with their 4-1 record overall which has them right at the top of the AFC South with one of the best records in the NFL. Their only loss this season was against the Rams on a last minute TD, but they could still be undefeated as that was a game where they really beat themselves. They are off a 40-6 win at home over the Raiders and they have been rolling over bad teams all season. Meanwhile, the Cardinals haven't looked good in their games this season with their 2-3 record overall which has them right at the bottom of the NFC West. They started the season 2-0 by beating up on some bad opponents, but they even struggled in those 2 wins and now they have lost 3 games in a row. They are coming off a terrible loss at home to the Titans in their last one and they blew a big lead in that game, giving the Titans their first win of the regular season. The Cardinals have been playing with fire all season, getting out to early leads the defense blowing those leads. They won't be able to do that against this Colts defense though, especially with the key players missing from their run game. The Colts are a better team at almost every position and they are going to show that in this game. The best way to place a bet here is on the Colts to cover the spread in this game. 

Cardinals Colts Prediction:  Our NFL Pick for Sunday, October 12, 2025 (1:00 pm ET start time) is Colts 41 Cardinals 13.

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Arizona Cardinals: 9-2 ATS as a road underdog of 7 points or less. 8-3 ATS in non-conference games. 4-0 ATS off an upset loss as a favorite. 6-2 OVER after a loss by 6 or less points. 

Indianapolis Colts: 3-8 ATS in non-conference games. 3-6 ATS after scoring 30 points or more last game. 5-1 OVER as a favorite of 3.5 to 9.5 points. 11-6 OVER after playing a game at home. 6-3 OVER when playing against a bad team (Win Pct. 25% to 40%).

Arizona Cardinals:  D. Robinson (DL) Injured - Pectoral. K. Murray (QB) Injured - Foot. K. Beachum (OG) Injured - Rest. E. Brown (OG) Injured - Hamstring. W. Hernandez (OG) Injured - Knee. Z. Jones (WR) Injured - Knee. M. Melton (CB) Injured - Hamstring. C. Simon (LB) Injured - Knee. J. Williams (OG) Injured - Foot. M. Wilson Sr. (LB) Injured - Ankle. W. Johnson (CB) Injured - Groin.

Indianapolis Colts:  K. Moore II (CB) Injured - Achilles. G. Stewart (DL) Injured - Biceps. B. Smith (OT) Injured - Rest. T. Lewis (DL) Injured - Illness. A. Pierce (WR) Injured - Concussion. T. Goodson (RB) Injured - Groin.

“Obviously, very disappointing. Felt like we had multiple chances to put away the game, all three phases, and we didn't do that. Collectively, we have to do a better job. Until we do a better job, we're going to keep losing.” - Jonathan Gannon after his team’s loss against the Titans in their last game. 

“I think the guys are playing at a high level right now, they’re playing together. (Taylor) is the best back in the league right now. Credit to him, credit to the O-line. It starts up front, but he’s just seeing it while he’s running hard.” - Shane Steichen after his team’s win against the Raiders in their last game. 

WR Harrison Jr., Marvin

WR Jones, Zay 

WR Wilson, Michael 

TE McBride, Trey

QB Murray, Kyler

RB Carter, Michael

WR Pittman Jr., Michael

WR Mitchell, Adonai

WR Downs, Josh

TE Warren, Tyler

QB Jones, Daniel

RB Taylor, Jonathan

Passing: Kyler Murray (962)

Rushing: Kyler Murray (173)

Receiving: Marvin Harrison Jr. (306)

Touchdowns: James Conner (2)

Passing: Daniel Jones (1,290)

Rushing: Jonathan Taylor (480)

Receiving: Tyler Warren (307)

Touchdowns: Jonathan Taylor (7)

Coaches:

Arizona Cardinals: Jonathan Gannon (3rd season)

Indianapolis Colts: Shane Steichen (3rd season)