Colts vs Cardinals Prediction 10/12/25 NFL Picks Today

The Arizona Cardinals and the Indianapolis Colts meet Sunday in NFL action from Lucas Oil Stadium. Here’s a Colts vs Cardinals prediction. We will look at this from a betting perspective and determine the best Colts vs Cardinals pick.

Arizona Cardinals Betting Preview

The Cardinals were able to win their first two games of the season—but they were both pretty close calls. Arizona powered past the New Orleans Saints 20-13 in the opener, then took out the Carolina Panthers 27-22 in game two. The next pair were both tight losses however, as the Cardinals fell to the San Francisco 49ers 16-15 and the Seattle Seahawks 23-20. In the loss to the Seahawks, the Cardinals gave up 384 yards total with 229 passing yards, 20 first downs and 6-of-13 on third-down tries. On offense Arizona mustered 253 total yards with 4.0 yards per play in the defeat.

In their Sunday game versus the Tennessee Titans, the Cardinals held a 21-6 edge by halftime and maintained that score through the third quarter. Arizona gave up 16 unanswered points in the final frame however, resulting in an embarrassing home loss 22-21. QB Kyler Murray was 23-of-31 for 220 yards while also rushing for 25 yards and a score. Emari Demercado carried three times for 81 yards to top the ground attack, and Marvin Harrison Jr. had four catches for 98 yards in the losing effort.

Indianapolis Colts Betting Preview

Over on the Colts’ side, they kicked off the season on a hot streak, flexing their offensive muscles in a trio of wins. Indianapolis blew out the Miami Dolphins 33-8 in their opener then eked past the Broncos 29-28 before another win over the Tennessee Titans 41-20. Game four was Indy’s first loss of the season however, as they dropped a road game to the Los Angeles Rams 27-20. The Colts offense gathered 333 total yards and 17 first downs along the way but also went just 4-of-12 on third downs and had three turnovers. The 11 penalties for 88 yards didn’t help the Colts’ cause either.

Matched up against the Raiders last weekend, the Colts faced a 3-0 deficit by the end of the first quarter but it didn’t last long. Indy scored 20 points in each of the next two quarters, eventually cruising to the blowout win 40-6. Daniel Jones was great on 20-of-29 passing for 212 yards and two touchdowns. Tops in rushing was Jonathan Taylor with 17 carries for 66 yards and three touchdowns, and Ashton Dulin had the top spot among the receivers with two catches for 55 yards in the victory.

Arizona Cardinals @ Indianapolis Colts Betting Trends: Week 6

Why the Indianapolis Colts will win

• The Colts have won each of their last 10 games as home favorites against opponents on a losing streak.
• The Cardinals have lost five of their last six road games.
• The Colts have covered the spread in each of their last five games in October.
• The Cardinals have failed to cover the spread in each of their last three Week 6 games.
• The Cardinals have lost the first quarter in each of their last four road games in October.
• The Colts have scored the first touchdown in each of their last four games as favorites.
• The favorites have won the first half in each of the Cardinals’ last seven games.

Why the Arizona Cardinals will win

• The Colts have lost each of their last six games against NFC opponents on a losing streak.
• The Cardinals have won four of their last five games as underdogs against AFC opponents.
• The Cardinals have covered the spread in each of their last six games as underdogs against AFC opponents.
• The Colts have failed to cover the spread in each of their last four games against NFC opponents.
• The Colts have lost the first quarter in four of their last five October games as favorites.
• The Cardinals have scored the first touchdown in seven of their last eight games against AFC opponents.
• The Cardinals have won the first half in each of their last four Week 6 games against AFC opponents.

Total Points Facts

• Each of the Cardinals’ last five games as underdogs have gone UNDER the total points line.
• Each of the Colts’ last four games in October have gone UNDER the total points line.

Indianapolis Colts Player Prop Facts

• Jonathan Taylor has scored two or more touchdowns in each of the Colts’ last four games against teams on a losing streak.
• Jonathan Taylor has scored at least one touchdown in each of his seven previous appearances with the Colts as home favorites against teams on a losing streak.
• Jonathan Taylor has recorded 118+ rushing and receiving yards in each of the Colts’ last four games as moderate favorites (-3.5 to -7.0 points).
• Daniel Jones has recorded 262+ passing yards in three of the Colts’ last four games following a win.
• Daniel Jones has recorded 26+ rushing yards in each of his last seven appearances with his team as a favorite against NFC opponents.
• Michael Pittman Jr. has recorded 63+ receiving yards in each of the Colts’ last eight games as favorites following a win.
• Daniel Jones has recorded 22+ completions in seven of his last eight appearances following a win.
• Heading into Week 6, Jonathan Taylor ranks 1st in the NFL in rushing yards (480) this season.

Arizona Cardinals Player Prop Facts

• Kyler Murray has recorded 229+ passing yards in each of the Cardinals’ last four October road games against AFC opponents.
• Kyler Murray has scored a touchdown in each of the Cardinals’ last three road games against AFC South opponents.
• Kyler Murray has recorded 32+ rushing yards in each of the Cardinals’ last six games as underdogs following a loss.
• Zay Jones has recorded 10+ receiving yards in each of his last eight road appearances against AFC South opponents.
• Kyler Murray has recorded 23+ completions in each of the Cardinals’ last seven games following a loss.
• Heading into Week 6, Josh Sweat ranks T3rd in the NFL in sacks (5.0) this season.

Matchup/League Facts

• Colts – one different players have recorded 100+ rushing yards in a game this season – equal-most in the NFL, heading into Week 6.
• Colts – seven different players have recorded 50+ receiving yards in a game this season – most in the NFL, heading into Week 6.
• Heading into Week 6, the Cardinals rank T1st in the NFL in 4th down percentage (100.0%) this season.
• Heading into Week 6, the Cardinals rank 1st in the NFL in Q3 opponent points per game (1.8) this season.

Colts vs Cardinals Prediction

I’m staying with the Colts. Indianapolis coughed up nine penalties for 77 yards last weekend in their home victory over the visiting Raiders, but that’s about the only thing to complain about in that matchup. The Colts posted 317 total yards (221 passing) with 5.6 yards per play, 24 first downs and a nice 8-of-10 effort on third downs—not to mention no turnovers—on offense in their latest win. The defense showed up as well with 296 yards, 22 first downs and 4.6 yards per play allowed along with two interceptions. After a couple of close games in the last few weeks, it was nice to get another relative blowout victory if you’re a Colts fan.

As for Arizona, they’ve got to get their ugly loss to the listless Titans in the rearview mirror—and quickly. The Cardinals lost three fumbles in that one, clearing the way for just 16 first downs along the way. The eight penalties didn’t help matters, either. That makes 21 or fewer points in four of five games so far this year for Arizona (27 in the outlier). Defensively the team is doing pretty well otherwise; they’ve got to clear up the mistakes on offense, though.