Arizona Cardinals vs. Indianapolis Colts Prediction and Picks – Sunday, October 12, 2025
Use Code SSWC The Indianapolis Colts will host the Arizona Cardinals in Week 6 of the 2025 NFL season, and we'll preview the lines and odds in our Cardinals vs. Colts prediction. Indy is coming off an emphatic 40-6 win over the Las Vegas Raiders in Week 5, while the Cardinals will look to recover after a meeting with the Tennessee Titans got away from them in embarrassing fashion. Kickoff is set for 1:00 PM ET on Sunday, October 12.
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How will the Cardinals respond after embarrassing Titans loss?
The Arizona Cardinals looked fine, if not great, early in their meeting last week with a 0-4 Tennessee Titans team. They were up 7-0 within five minutes of kickoff–second-year receiver Marvin Harrison Jr. high-pointed a pass from quarterback Kyler Murray 44 yards down the field, nearly securing a touchdown through double-coverage and illegal contact from cornerback Jalyn Armour-Davis before a replay official ruled him down at the 1-yard line. Harrison had two more catches on the next drive, catching a back-shoulder throw against Armour-Davis and beating zone coverage in the middle of the field for a combined 36 yards, helping the Cardinals to go up 14-3 as the first quarter ended. The offense was humming because of that connection, and they were getting enough from Michael Carter as a lead back mere weeks after his promotion from the practice squad. When the Cards went up 21-3 after recovering a Titans fumble in the second quarter, the game looked well on its way to a decisive, boring win for Arizona.
On the contrary, one of the biggest stories of Week 5 was how the Cardinals floundered the game away–they didn't score again, and the Titans kicked a 29-yard field goal as time expired to win 22-21, giving them their first win of the season and dropping the Cards to 2-3. It's not that the Titans looked great–they gave away plenty of drives between receivers dropping open passes and rookie quarterback Cam Ward attempting ill-advised throws. The Cardinals were still up 21-6 at the start of the fourth quarter, when third-year back Emari Demercado became the latest player to voluntarily fumble away a touchdown at the one-yard line after running 71 yards. Head coach Jonathan Gannon was fined $100,000 by the team and issued a public apology for his on-field response.
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The Titans took possession on the 20-yard line after the touchback, then scored on three straight drives while holding the Cardinals' offense to 16 total yards. Rookie safety Dadrion Taylor-Demerson nearly iced the game when he picked off a deflected pass from Ward, but he fumbled on contact with the ground–the ball rolled forward, allowing Titans receiver Tyler Lockett to recover it in the endzone for a touchdown.
It wasn't a great day at the office for anybody in Arizona. Murray finished the game having completed 22 of 31 passes for 220 yards, taking three sacks, committing an egregious grounding penalty in the second quarter, losing a fumble in the third quarter, and losing track of Harrison after the first couple of drives. Demercado's would-be touchdown was the team's only run of the game to eclipse 20 yards; fellow backs Carter and Bam Knight both averaged fewer than three yards on a combined 22 carries. If they don't look substantially better in Week 6, the game won't look nearly as close on the scoreboard.
On the injury front, Murray returned to practice on Friday after missing the first two days. He's listed as questionable with a foot injury.
Colts continue early-season roll against overmatched Raiders
The Indianapolis Colts steamrolled the Raiders in Week 5, but the game looked like it'd be much closer in the first 15 minutes. Indy went three-and-out on their first possession, setting the Raiders up for a drive that ran 15 plays–and nearly the entire first quarter–before ending in a 24-yard field goal from kicker Daniel Carlson. The Colts were a holding penalty away from responding with a 98-yard return touchdown from Ashton Dulin, but they finished the drive with a touchdown anyway after quarterback Daniel Jones and the offense went 83 yards on 16 plays. They notched their second touchdown drive of the quarter after blocking a Raiders punt, then a third after second-year edge Laiatu Latu dropped into coverage and caught a deflected pass–ending a Raiders drive that'd advanced to the Colts' 11-yard line. The Colts put on a masterful drive to close the quarter, running 16 plays and advancing 63 yards for a touchdown in just under four minutes.
The third quarter went much the same–the Colts' offense scored three touchdowns on three drives while their defense allowed 25 total yards, ending one Raiders drive with an interception from cornerback Mekhi Blackmon and another with a 4th-and-1 stop against rookie back Ashton Jeanty. By the Colts' first drive of the fourth quarter, they were up 40-6 and letting Anthony Richardson play out the game at quarterback. Jones finished the game 20-29 for 212 yards, good for 69.0% completion percentage and 7.31 yards per attempt, with two touchdowns and no interceptions or sacks. Jonathan Taylor led the backfield with 66 yards and three touchdowns on 17 carries. The defense racked up six TFLs, four sacks, eight pass defenses, and two interceptions against quarterback Geno Smith and the Raiders offense, who were held to six points despite making four redzone appearances and finishing the game with only 21 fewer yards than the Colts' offense.
Indy enters Week 6 tied for the best record in the NFL at 4-1, and they lead the AFC with 163 points scored. Taylor leads the league with both 480 yards and six touchdowns on the ground, while Jones ranks third in passing yards (1,290) with a 71.3% completion percentage. Barring injury, this team is shaping up to be a high-end playoff contender and a tough matchup for anyone down the stretch.
In terms of key injuries, CB Kenny Moore (Achilles) is out.
Cardinals vs Colts pick
Spread Pick for Cardinals vs Colts
- Cardinals +7.0 (-102) (4 Units)
There's a familiarity angle here between Cardinals head coach Jonathan Gannon and Colts head coach Shane Steichen–both were in Philadelphia from 2021-22, coordinating opposite sides of the ball, before being hired to their current roles in the same offseason. Steichen currently oversees one of the league's most prolific offenses; Gannon leads a Cardinals team that–despite their record–has lost three games by a combined five points and hasn't given up more than 23 points to any of their opponents. The Colts rocked the Raiders on the scoreboard, but the yardage and conversion rates reflect a game that was blown out on the margins and could've easily been much closer. This game should be the Cardinals' biggest challenge yet, but I'd expect them to keep things close, putting last week's debacle as far behind them as possible.
Over/Under Pick for Cardinals vs Colts
- Under 47.0 (-110) (4 Units)
The Team Total Under is 3-2 in both of these teams' games, and has hit in all three Colts games so far where the pregame total was above 43 points. It's the highest pregame total line the Cardinals have seen this season, a week after the Titans needed an unlikely game-winning field goal to beat them 22-21 and hit the over on a 41.5 line. I'd expect the Colts to come down a bit from last week's blowout and play a closer, lower-scoring game.
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