My Lions vs. Cardinals prediction is laying 5.5 points with Detroit, whose ferocious pass rush could turn Arizona's battered offensive line into a revolving door.
With Cardinals left tackle Paris Johnson sidelined, the Lions have a major edge in the trenches heading into today's 4:25 p.m. ET kickoff at State Farm Stadium on FOX. Here's why I'm backing Detroit to cover in my latest NFL picks for Week 5.
TOP Pick
Lions vs Cardinals prediction: Lions -5.5
I recommended Detroit at a better price earlier this week, but I'm still willing to trade the Detroit Lions -5.5 up to -6.
Detroit's pass rush has a strength-on-weakness advantage against the Arizona Cardinals' offensive line. According to ESPN, Arizona's offensive line ranks 31st in pass-blocking rate, while the Lions rank fourth in pass-rush win rate. The Cardinals also placed starting left tackle Paris Johnson on season-ending injured reserve.
The situational angle helps, too. Under head coach Dan Campbell, Detroit is 13-4-1 against the spread (ATS) as a favorite following a loss with a +6.8 spread differential.
I'm putting stock in this trend because Campbell has proven he can get the Lions to take their anger out on inferior teams after a loss.
COVERS INTEL: Since 2025, the Cardinals are 1-6 ATS as a home underdog with an 8.2 spread differential.
Lions vs Cardinals combo
I'm expecting Detroit to control this game without needing a shootout. I have the Lions winning 29-20, which gives them enough margin to cover while keeping the total comfortably below 54.5.
Detroit defensive coordinator Kelvin Sheppard also blasted the media earlier this week, and I expect his defense to back him up on the field today.
If the Lions play from ahead, they can lean on their running game in the second half, bleed the clock, and make Arizona chase points against Detroit's aggressive pass rush. That same offensive control should give Lions tight end Sam LaPorta opportunities near the goal line.
Arizona already struggles covering tight ends, and Detroit's other weapons demand so much attention that LaPorta can find favorable matchups over the middle. A methodical Lions win with LaPorta finding the end zone fits all three legs nicely.
Lions vs Cardinals combo
- Lions -5.5
- Under 54.5
- Sam LaPorta anytime touchdown
Lions vs Cardinals touchdown scorer: Sam LaPorta
Jahmyr Gibbs and Amon-Ra St. Brown command so much attention that it’s difficult for defenses to key in on tight end LaPorta, who is a game-breaker in his own right. LaPorta has caught a touchdown in two games this season, and the Cardinals have surrendered the fourth-most fantasy points to the position.
LaPorta is Pro Football Focus’ sixth-ranked tight end, and the middle of Arizona’s defense is vulnerable in pass coverage. The Cardinals' starting linebackers, Mack Wilson Sr. and Jack Gibbens, along with safety Budda Baker, all have failing pass-coverage grades.
Lions vs Cardinals player prop: Jeremiyah Love 45+ rushing yards
Given Jeremiyah Love's projected role, we're getting an awesome price on his rushing prop, which is playable up to 50.5 yards. The average opposing starting running back has been lined at 65.5 rushing yards against Detroit, with two clearing their respective totals and another finishing with 46 yards.
Love was the first running back selected in the 2026 NFL Draft at No. 4 overall, so Arizona has every reason to feature him. He's averaging roughly 14 carries and 55.8 rushing yards per game, including outings of 90 and 63 yards over the last two weeks.
The matchup is even better. According to Pro.NFL.com, Detroit is tied for an NFL-worst +1.0 rushing yards over expectation allowed per carry and gives up the third-most yards before contact per carry.
Want more NFL player props? Check out our NFL player prop projections!
- Top picks: 5-8, -3.55 units
- Combos: 4-9, +8.07 units
Lions vs Cardinals odds
For help understanding probabilities, see our odds calculator.
- Spread: Lions -5.5 | Cardinals +5.5
- Over/Under: Over 54.5 (52%) | Under 54.5 (53%)
- Moneyline: Lions 72% | Cardinals 31%
For the full slate of NFL matchups, check out our NFL odds board!
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Lions vs Cardinals weather
This game is being played in a dome.
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Lions vs Cardinals trend to know
The Lions are an NFL-best 13-5 ATS as a home favorite since Dan Campbell took over in 2021. Find more NFL betting trends for Lions vs. Cardinals.
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How to watch Lions vs Cardinals
| Location | State Farm Stadium, Glendale, AZ |
| Date | Sunday, Oct. 11, 2026 |
| Kickoff | 4:25 p.m. ET |
| TV | FOX |
Lions vs Cardinals latest injuries
Check out our NFL injuries page for updates on every team.
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