Lions vs. Cardinals odds, picks, prediction, spread, line: NFL Week 5 start time, betting preview, best bets

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Here's everything bettors need to know for Lions vs. Cardinals in NFL Week 5 action

Oct 11, 2026 at 5:00 am ET • 2 min read

One of the more intriguing NFL Week 5 games takes place in the desert, where the Arizona Cardinals host the Detroit Lions. The Cards are 1-3 and have dropped three straight since their win over the Chargers in Week 1, while Detroit is 2-2 after falling to Carolina in a shootout on Sunday Night Football. Neither defense has impressed this year, so this one has the makings of a high-scoring affair, if you're into that sort of thing. Kickoff from Arizona is set for 4:25 p.m. ET. DraftKings Sportsbook lists the Lions as 4.5-point favorites, and the Over/Under is set at 54.5. Spend $5+ on Lions-Cardinals in Week 5 with the latest DraftKings promo code and get $150 in bonus bets:

We'll break down the latest Lions vs. Cardinals odds from DraftKings Sportsbook and deliver our best bets for the contest with help from the SportsLine Projection Model. The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on betting sites on top-rated NFL picks since its inception.The model entered Week 5 of the 2026 NFL season on a 55-44 run on top-rated picks dating back to 2024. Anybody following its picks at NFL betting sites could have seen strong returns.  

Lions vs. Cardinals betting odds (via DraftKings)

Lions vs. Cardinals money line:	Lions -218, Cardinals +180
Lions vs. Cardinals over/under:	54.5 (Over -112, Under -108)
Lions vs. Cardinals spread:	Lions -4.5

Lions vs. Cardinals betting preview

These defenses need a lot of work done. The Lions are giving up the most yards and passing yards in the NFL this season and are 31st in scoring defense at 31.8. Only New Orleans is worse.

That's music to the ears of Jacoby Brissett and the Cardinals. Arizona has its faults, to be sure, but it has a lot of playmakers on offense. Tight end Trey McBride has 46 targets and has converted those looks to 33 catches, 242 yards and two touchdowns. Michael Wilson has 258 yards and a score this year, Marvin Harrison Jr. found the end zone last week and the team has an intriguing running back room with Jeremiyah Love and Tyler Allgeier. 

The Cardinals' defense is also suspect, and the Lions have one of the best offenses in the NFL this year. Arizona is 29th in scoring defense and the Lions are fifth in points per game at 29.8. Jared Goff has nine touchdowns to no interceptions, and Jahmyr Gibbs has seven total touchdowns on the year. 

With poor defenses and good to great offensive personnel on each sideline, points are to be expected, as evidenced by an Over/Under betting line of 54.5 at DraftKings. Wager on NFL Week 5 games, including Lions-Cardinals, with the latest BetMGM bonus code CBSSPORTS to get up to $1,500 in bonus bets:

Lions vs. Cardinals picks, prediction

Lions -4.5

The SportsLine model is big on the Lions here. Detroit is a 4.5-point spread betting favorite despite being on the road, and the Lions have the makings of the NFL's best and most balanced offense. The issue is the defense, which has yet to allow fewer than 24 points in a single game this year. The Cardinals' offense has intriguing talent, but it's been a bit inconsisent, scoring 26, 7, 30 and 24 points this year. Can Arizona keep up? The model doesn't think so, with Detroit covering in roughly 60% of simulations.