Arizona Cardinals (2-3)  vs. Indianapolis Colts (4-1) Preview, Prediction & Odds | Week 6, 2025

Colts
Arizona Cardinals (2-3) at Indianapolis Colts (4-1)
Game Details: Sunday, October 12 1 p.m. EST
Location:  Lucas Oil Stadium
Where to Watch: FOX

Week 6 Matchup

The Indianapolis Colts enter Week 6 riding high with a 4-1 record and the NFL’s second-highest scoring offense. Meanwhile, the Arizona Cardinals arrive in Indianapolis nursing wounds from their third consecutive last-second loss, a devastating 22-21 collapse against the previously winless Tennessee Titans that has left players and coaches searching for answers.

This matchup presents a fascinating contrast between a surging Colts team that has found its offensive rhythm under former New York Giants quarterback Daniel Jones and a Cardinals squad that has shown flashes of brilliance but continues to stumble in crucial moments. The emotional toll of Arizona’s recent failures will be tested against an Indianapolis team that seems to have all the pieces clicking at the right time.

Betting Odds

Team Spread Money Line Total
Arizona Cardinals+7.5+295Over 46.5
Indianapolis Colts-7.5-370Under 46.5

** Odds Subject to Change – Courtesy of FanDuel**

Tale of The Tape

Arizona CardinalsTeam Stats – Avg Per GameIndianapolis Colts
20.6Points Per Game32.6
170.2Passing Yards Per Game253
118.2Rushing Yards Per Game128.2
19.2Opponents Points Per Game Allowed17.8
254.2Opponents Pass Yards Allowed 217.0
92.4Opponents Rush Yards Allowed 98.0

Statistics from various online sources and courtesy of ESPN

Key Details

Indianapolis Colts quarterback Daniel Jones (17) throws Sunday, Oct. 5, 2025, during a game against the Las Vegas Raiders at Lucas Oil Stadium in Indianapolis.

Arizona Cardinals

The Cardinals’ struggles have been particularly painful given how close they’ve come to victories. In their three losses this season, Arizona has been defeated by a combined total of just five points, with each game ending on a walk-off field goal. The most recent disaster against Tennessee featured running back Emari Demercado dropping the ball before crossing the goal line on what should have been a 72-yard touchdown.

Despite the recent setbacks, outside linebacker Josh Sweat has been a bright spot with five sacks through five games, the most he’s recorded in the first five games of his career.

Said Sweat: “We are doing anything to throw it away at this point. It’s killing me. I’m going to be real, it’s killing me because I see what this team can be. First half, you can see it.”

Indianapolis Colts

The transformation of Indianapolis under coach Shane Steichen has been nothing short of remarkable this season. Daniel Jones has completed 71% of his passes for 1,290 yards, ranking fifth and third, respectively, in the NFL. His chemistry with rookie tight end Tyler Warren has opened up entirely new dimensions for the offense. Warren, drafted 14th overall in April, leads rookie tight ends with 23 receptions for 307 yards and has become Steichen’s Swiss Army knife.

“It’s a very nice luxury to have because he’s so talented and has so many different skill sets,” Steichen said.

The former Penn State star has scored rushing touchdowns, made key blocks, and even attempted his first NFL pass attempt. Running back Jonathan Taylor has been equally impressive, with the offensive line protecting Jones so well that the league’s longest active sack streak ended at 39 games during their 40-6 demolition of Las Vegas.

Prediction

kyler murray
Jan 5, 2025; Glendale, Arizona, USA; Arizona Cardinals quarterback Kyler Murray (1) against the San Francisco 49ers at State Farm Stadium. Mandatory Credit: Mark J. Rebilas-Imagn Images

A few weeks ago, we wrote that Arizona is the worst 2-0 team. Then the worst 2-1 team. Now the Cardinals are 2-3, and they have done nothing to change the thinking that they are bad. Until Kyler Murray and the Cardinals show some life, something that resembles a disciplined and talented team, they will not be picked, even with a large point spread. And, the Colts are pretty darn good.

Final Pick

Indianapolis Colts  -7.5

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