Dan Johnson takes you through his preview, prediction, and pick for NFL Week 6’s game between the Indianapolis Colts and the Arizona Cardinals.

Lucas Oil will bump and the sound will linger, because this matchup carries pivot energy. The Indianapolis Colts arrive at 4-1 with a scoring engine that rarely sputters. The Arizona Cardinals stagger in at 2-3 after three straight one-score defeats that gnaw, a five-point aggregate that stings. The headline flips everything: Jacoby Brissett, official starting quarterback, starts for Arizona. That change tilts the geometry and sharpens the handicap. Indianapolis is 3-0 at home and has covered all three. But is the late pivot something that might take the Colts by surprise at all? Below is my prediction for NFL Week 6’s game between the Indianapolis Colts and the Arizona Cardinals.

Here’s how I’ll play it. I’ll be pumping out these predictions for individual games all season, with plenty of coverage here on DraftKings Network. Follow my handle @dansby_edits for more betting plays.

Indianapolis has hammered opponents with balance. Daniel Jones completes 71.3% and has thrown for 1,290 yards with six touchdowns and two interceptions. He averages 8.6 yards per attempt with a 105.1 rating. The offense hums at 32.6 points per game and stacks 253.0 passing yards with 128.2 rushing yards. The unit averages 381.2 total yards, fourth in the league. The line has allowed only four sacks all season and the offense has committed just three turnovers. Jonathan Taylor leads the league with 480 rushing yards and six touchdowns, and he adds 16 catches for 133 yards. The Colts protect their defense with rhythm and then clamp down. They allow 17.8 points per game, 217.0 passing yards, and 98.0 rushing yards, and they have allowed only two rushing touchdowns. The defense owns eight takeaways and just throttled Las Vegas with four sacks, six tackles for loss, and eight pass breakups.

Arizona protects the scoreboard better than chatter suggests. The Cardinals allow 19.2 points per game and just 92.4 rushing yards. They have tightened third quarters to a whisper at 1.8 opponent points per game. They have been perfect on fourth down at 100.0%. Trey McBride supplies 29 catches for 275 yards and a touchdown. Marvin Harrison Jr. posts 306 yards at 15.3 per catch and has turned four of six 20+ air-yard targets into 136 yards. Mack Wilson stacks 41 tackles with two tackles for loss as the front bristles. Josh Sweat adds 5.0 sacks, and Dadrion Taylor-Demerson has two interceptions. No opponent has topped 23 points against Arizona.

The Colts’ early-down efficiency forms the spine. They own the league’s best early-down success rate, and that steadiness sets Taylor’s tempo. Arizona sits 31st by that same measure, and that gap matters when possessions compress. Michael Pittman Jr. has produced 26 catches, 273 yards, and four touchdowns, and Tyler Warren adds 23 catches for 307 yards. Seven different Colts have posted 50+ receiving yards in a game this season, which stretches coverage rules. Against the Raiders, Indianapolis went 8-for-10 on third down and never trailed after the first quarter. The Colts have scored the first touchdown in each of their last four games as favorites.

The Cardinals must lean into Brissett’s operational calm. Jacoby Brissett has recorded 233+ passing yards in three of his last four October appearances as a road underdog. He has reached 20+ rushing yards in three of his last four as a road underdog against AFC South opponents. Arizona’s offense has averaged 20.6 points per game with 170.2 passing yards and 118.2 rushing yards for 288.4 total. The passing game has sagged at 5.3 yards per attempt, and the offense has produced 50 first downs with 41 penalties for 273 yards. Arizona has scored 21 or fewer in four of five games. That profile pairs with a pass defense that has bled 254.2 yards per game, so the coverage group must squeeze windows and trust the sturdy run fit to keep Taylor from stamping drives.

Brissett’s installation should shift Arizona from Murray’s scramble-chaos to more scheduled snaps—huddles, hard counts, full-field progression work, and check-with-me runs—creating looks Indianapolis hasn’t prepped for on tape, fostering sustained drives, milking clock, and leveraging veteran poise in end-of-half management.

Cardinals vs. Colts pick, best bet

The Cardinals lost the last three by a combined five points and kept those games within one score into the fourth. They have traveled well defensively and carry that 19.2 points allowed baseline. They are 7-1 against the spread in their last eight against the AFC and 6-2 against the AFC South. The refutation is Indianapolis’ continuity and composure. The Colts are 3-0 at home, 4-1 against the spread, and 3-0 when favored on the moneyline. They have scored 163 points through five games and rarely beat themselves. When Jones follows a win, he stays efficient; he has recorded 22+ completions in seven of his last eight in that spot. Indianapolis also ranks third in scoring defense and hasn’t allowed more than 27 all year.

The Cardinals are 2-3 against the spread, and the Colts are 4-1 against the spread, with Indianapolis 3-0 against the spread at home. Each of the Cardinals’ last five games as underdogs has gone under the total. Each of the Colts’ last four October games has gone under. Indianapolis games average 46.3 combined points; Arizona games average 43.9. The dome cleans the air, but both teams favor clock-eating drives over reckless shot-trading.

The over case isn’t imaginary, though. Indianapolis scores 32.6 per game and lives at 253.0 passing and 128.2 rushing; Taylor has six touchdowns; and Indy’s secondary has sprung 12 explosive passes in two weeks—exactly the lane where Harrison Jr. can flip field position in one snap. If that shows up early, game state can force Arizona to press and give you late-total volatility that threatens an under.

Final score projection: Colts 27, Cardinals 17. I still prefer the under because the structural numbers (both defenses’ points allowed, Arizona’s third-quarter clamp, and the Brissett tempo shift) all press the possession count down and convert more drives into field goals. Arizona squeezes pace with 19.2 points allowed, 92.4 rushing yards allowed, a 100.0% mark on fourth down, and just 1.8 opponent points in third quarters.

Best bet: Colts vs. Cardinals u46.5 total points (-120)

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For a prop lean, Trey McBride over 6.5 receptions (−120). The usage backs it—5.8 receptions on 8.4 targets so far—and Brissett’s history in road-dog spots points to a high-percentage, first-read rhythm that funnels to the underneath option. The Colts just played without Kenny Moore II, and that short/intermediate seam is where Arizona can stitch 8–10 play marches that fit both the matchup and your projected score.

Best prop lean: Trey McBride o6.5 receptions (-120)

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