Game Preview of Arizona Cardinals @ Indianapolis Colts. Week 6 of 2025 NFL Season
Arizona heads to Lucas Oil Stadium on Sunday to face Indianapolis. Kickoff is 1:00 PM ET in Week 6. The Colts are one of the league’s hottest teams, while the Cardinals are trying to steady the ship after a rough stretch.
The big question is Kyler Murray’s health. He is listed as questionable with a leg issue. If he cannot go or is limited, Jacoby Brissett would step in. Arizona also has several offensive linemen on the report and James Conner is on injured reserve, which strains the run game and pass protection.
Indianapolis is thriving with clean pockets and efficient drives. The Colts rarely give up sacks and convert third downs at a high rate. That formula pairs well with Jonathan Taylor’s burst and a passing game that hits chunk gains without many negative plays.
The Colts have injuries in the secondary, so communication on the back end will matter. Even so, their defense has kept a lid on explosive passes, and their offense sustains long marches. That makes Arizona’s red zone execution and quarterback mobility the swing factors.
| Date | Opponent | Result | ATS | O/U |
|---|---|---|---|---|
| 2025-10-05 | vs LV | W 40-6 | W +7.0 | u46.5 |
| 2025-09-28 | @ LAR | L 20-27 | L 3.5 | u49.5 |
| 2025-09-21 | @ TEN | W 41-20 | W +-6.0 | o43.5 |
| 2025-09-14 | vs DEN | W 29-28 | L -2.5 | o43.5 |
| 2025-09-07 | vs MIA | W 33-8 | W +1.5 | u47.5 |
| 2025-01-05 | vs JAX | W 26-23 | W +3.5 | o45.5 |
| 2024-12-29 | @ NYG | L 33-45 | L -7.5 | o40.5 |
| 2024-12-22 | vs TEN | W 38-30 | W +4.0 | o42.5 |
| 2024-12-15 | @ DEN | L 13-31 | L 4.5 | o43.5 |
| 2024-12-01 | @ NE | W 25-24 | W +-2.5 | o41.5 |
Colts pass protection travels. A 2.6% sack rate allowed (91st percentile) lets Daniel Jones work through progressions and keeps the playbook open.
Arizona’s offense has struggled to create explosives through the air. Their explosive pass rate is 4.0% (6th percentile), which fits the Colts’ strength in limiting deep shots (explosive passes allowed 5.4%, 83rd percentile).
Indianapolis thrives on schedule. The Colts convert 46.6% on third down (94th percentile), while Arizona’s defense is strong on third down stops (64.2%, 78th). This is the core chess match.
If Murray is limited, Arizona’s shotgun and no-huddle looks may lean quick-game. They rank high in shotgun tendency (57.7%, 81st) and use pace spots (no-huddle 8.4%, 70th) to spark drives.
The Colts’ defense generates takeaways at a strong rate (2.3%, 86th). Arizona’s defense lags in that area (0.9%, 17th), so turnover margin tilts toward Indy.
Multiple Cardinals OL are questionable. That matters against Indy’s steady pressure-to-sack conversion (6.9%, 66th) and could affect Arizona’s third down rhythm.
Spread angle: Colts -5.5 at -172 is expensive. Colts -6.0 at -159 offers a better price if you can stomach the extra half point.
Total frame: 47.5 is the closest listed number to mid-high scoring. Over 47.5 is +102 and Under 47.5 is -123, reflecting modest lean to the Under.
QB legs as a lever: Daniel Jones Over 17.5 rushing yards is -115. Low sack rate creates scramble windows that can cash on a few plays.
Workhorse spot: Jonathan Taylor Over 89.5 rushing yards is -122. Arizona’s defense allows a high rate of explosive runs, which can flip a yardage prop.
Volume receiver: Michael Pittman Jr. Over 53.5 yards is -119. Indy’s explosive pass rate is solid and sustained drives feed targets.
Anytime scorer: Jonathan Taylor is -233 to score. Pricey juice, but Indy’s third down and long-drive strengths point to red zone volume.
Indianapolis brings a clear identity. Protect the quarterback, win third down, and finish drives. That style has produced long, efficient possessions and limited mistakes. At home, with a strong run game and a steady passing plan, the Colts set a high floor.
Arizona’s path runs through quarterback health and tempo. If Murray is close to full speed, his movement can challenge Indianapolis’ zone integrity and extend plays. If not, the Cardinals may need quick throws and schemed touches to stay ahead of the sticks.
On paper, the trenches and turnover profile tilt to the Colts. Their pass protection and takeaways have been difference-makers. Arizona’s injuries, especially up front and in the backfield, add volatility to their side.
Market-wise, the listed spread sits in the -5 to -6 range with a total around 47.5. Expect Indianapolis to lean on Taylor and sustained drives, while Arizona looks for pace and quarterback mobility to spark explosives. As always, account for juice and injury updates before placing any bets.
| Statistic | Offense | Rank | Defense | Rank | Advantage |
|---|---|---|---|---|---|
| Total Points | 163 | #2 | 96 | #27 | |
| Total Points Per Game | 32.6 | #2 | 19.2 | #4 | |
| Total Touchdowns | 17 | #4 | 9 | #5 | |
| Passing Touchdowns | 6 | #28 | 5 | #7 | |
| Rushing Touchdowns | 11 | #1 | 3 | #10 | |
| Other Touchdowns | 0 | #15 | 1 | #26 | |
| Total Kicking Points | 53 | #1 | 42 | #10 | |
| Total Two Point Conversions | 1 | #7 | 0 | #20 | |
| Kick Extra Points | 14 | #7 | 6 | #32 |
| Statistic | Offense | Rank | Defense | Rank | Advantage |
|---|---|---|---|---|---|
| Net Passing Yards | 1265 | #4 | 1271 | #4 | 🏈 |
| Net Passing Yards Per Game | 253 | #4 | 254 | #5 | |
| Passer Rating | 104 | #9 | 82.5 | #27 | |
| Passing Attempts | 153 | #20 | 207 | #32 | |
| Completions | 108 | #15 | 128 | #4 | |
| Completion Percentage | 70.6 | #5 | 61.8 | #6 | |
| Passing 1st downs | 63 | #5 | 68 | #30 | |
| Passing 1st Down % | 54.3 | #21 | 64.2 | #29 | |
| Longest Pass | 75 | #6 | 47 | #21 | |
| Passing Fumbles Lost | 1 | #12 | 1 | #15 | |
| Receiving Targets | 150 | #18 | 193 | #1 | |
| Receptions | 108 | #15 | 128 | #29 | |
| Receiving Yards After Catch | 562 | #11 | 514 | #14 | |
| YAC Average | 5.2 | #11 | 4.0 | #4 |
| Statistic | Offense | Rank | Defense | Rank | Advantage |
|---|---|---|---|---|---|
| Rushing Yards | 641 | #8 | 462 | #9 | |
| Rushing Yards Per Game | 128 | #9 | 92.4 | #25 | |
| Rushing Attempts | 146 | #3 | 120 | #11 | |
| Yards Per Rush Attempt | 4.4 | #17 | 3.9 | #26 | |
| Rushing 1st downs | 39 | #5 | 25 | #8 | |
| 20+ Yard Rushing Plays | 2 | #19 | 3 | #14 | |
| Long Rushing | 68 | #5 | 24 | #28 | |
| Rushing Fumbles | 2 | #19 | 3 | #14 | |
| Rushing Fumbles Lost | 0 | #21 | 1 | #18 |