Cardinals at Colts: Week 6 NFL Betting Preview
Sunday, October 12, 2025 – 1:00 PM ET – Lucas Oil Stadium
MyBookie Line: Colts -7 | Total: 46.5
Game Overview
The Indianapolis Colts (4-1) welcome the struggling Arizona Cardinals (2-3) to Lucas Oil Stadium in what shapes up as a prime opportunity for the home team to extend their impressive start. After dismantling the Las Vegas Raiders 40-6 last week, the Colts look to capitalize on facing another team in turmoil.
Arizona enters this matchup reeling from one of the most devastating collapses of the young season. Leading 21-6 against the winless Tennessee Titans, the Cardinals somehow managed to get outscored 16-0 in the fourth quarter and lost 22-21 on a last-second field goal. This marked their third consecutive loss decided by a field goal in the final moments—an unprecedented streak of heartbreak.
Quarterback Situation Adds Uncertainty
The biggest question mark heading into Sunday centers on Kyler Murray’s availability. The Cardinals quarterback is dealing with a foot injury and didn’t practice yesterday, with the team calling him day-to-day. While Murray did return to finish last week’s game against Tennessee—typically a positive sign for availability—his status remains uncertain. Should Murray be unable to go, Jacoby Brissett would make his first start against his former team, adding another layer of intrigue to this matchup.
Why the Colts Cover
Indianapolis has emerged as one of the NFL’s most explosive offenses through five weeks, averaging 32.6 points per game (2nd in the league). Daniel Jones has been exceptional, throwing for 1,290 yards while completing 71.3% of his passes—currently third among all quarterbacks in passing yards. The Colts’ offensive efficiency has been remarkable: just seven punts and three turnovers against 17 touchdowns through five games.
The matchup heavily favors Indianapolis when examining defensive statistics. Arizona’s defense ranks 22nd in total yards allowed and a troubling 28th against the pass. What makes these numbers even more concerning is the quality of quarterbacks they’ve faced: Spencer Rattler, Bryce Young, Mac Jones, Sam Darnold, and Cam Ward. Now they’re tasked with containing the league’s third-leading passer operating behind an offense that scored on six of eight drives last week.
Historical trends strongly support the home team. The Colts have won 10 straight games as home favorites against opponents on losing streaks. They’ve also covered the spread in their last five October games. Meanwhile, Arizona has dropped five of their last six road contests and failed to cover in their last three Week 6 appearances.
Model Prediction Aligns with Market
Our projection model forecasts a 28-14 Colts win. This two-touchdown margin reflects both the offensive disparity between these teams and Arizona’s recent struggles to maintain leads. The Cardinals have been outscored 39-15 in the fourth quarter during their three-game skid, demonstrating a troubling inability to close out games.
Teaser Opportunity
For those looking to add extra value, the Colts present an excellent teaser option. Taking them from -7 down to -1 with a six-point teaser provides significant cushion while still backing the clearly superior team. Consider pairing this with other strong plays from the weekend slate—the Eagles tonight, the Rams over Baltimore, or the Lions moving from +2.5 to +8.5 all offer attractive teaser legs.
Total Points Analysis
While the total sits at 46.5, recent trends suggest the under deserves consideration. Both teams have seen their recent games stay under the total—the Cardinals’ last five games as underdogs have all gone under, while the Colts’ last four October games have followed the same pattern. However, the Colts’ offensive firepower at home (averaging 38 points against bottom-half defenses) provides reason for caution on the under.
Key Statistical Edges
The Colts dominate several crucial statistical categories that typically correlate with both wins and covers:
- Offensive Balance: Indianapolis features seven different players with 50+ receiving yards in a game this season, the most in the NFL
- Red Zone Efficiency: Jonathan Taylor has scored at least one touchdown in his last seven home games as a favorite against losing teams
- Turnover Differential: The Cardinals have tied or lost the turnover battle in three of five games; they lost three fumbles against Tennessee
The Bottom Line
Everything points toward a comfortable Colts win and cover. They’re the superior team on both sides of the ball, playing at home against an opponent that just suffered a crushing defeat. Arizona’s potential quarterback uncertainty only strengthens the case for Indianapolis.
While the Cardinals have shown fight in close games—all five of their contests decided by seven points or fewer—their inability to finish games and protect the football makes them a poor bet as seven-point road underdogs. The Colts’ home dominance (3-0 with all covers this season) combined with their offensive explosion makes them the clear side.
Pick: Indianapolis Colts -7
Lean: Under 46.5
Best Bet: Colts -1 in a 6-point teaser