Lions vs Cardinals NFL Picks and Predictions

Our Lions vs Cardinals NFL picks and predictions cover the (2-2) Detroit Lions at the (1-3) Arizona Cardinals on Sunday, October 11th at 4:25 PM ET. Check out our full Week 5 NFL Schedule for odds and predictions on every game this week.

All of the odds, matchup grades, injury data, and betting trends referenced below come from HOF's sports betting research app, which tracks live lines and team/player data to help bettors make more informed decisions. For our top touchdown scorer prop picks and DFS plays in this game, check out our Lions vs Cardinals NFL Player Props and DFS Picks article.

Odds

Detroit is favored at -4.5 (-105) on the spread with a -218 moneyline, while Arizona sits at +4.5 (+104) on the spread and +213 on the moneyline. The total is set at 54.5, with the over priced at -104 and the under at -104 — the highest total on the Week 5 board outside the Monday night game, pointing toward a shootout.

Matchup Breakdown

Detroit's offense grades out among the best in the league against Arizona's defense, ranking 3rd in both Anytime TDs and Pass Yards, 6th in Rush+Rec Yards and Pass TDs, and 8th in Rush TDs. Arizona's defense is vulnerable, ranking 31st against Anytime TDs, 30th against Pass TDs, and 25th against Rush+Rec Yards, and Goff carries a B matchup grade with a projection of 303.5 passing yards and 2.3 touchdowns.

Arizona's offense also has a strong matchup, as Detroit's defense ranks dead last in the league against Rush+Rec Yards, Anytime TDs, and Pass Yards, and 31st against Pass TDs. J. Brissett carries an A+ matchup grade with a projection of 204.5 passing yards and 1.5 touchdowns, even though Arizona's own offense ranks 22nd in both Rush+Rec Yards and Pass Yards.

Injury Report

I. Pacheco (DET) – Back, Out (9/14).

R. Ya-Sin (DET) – Hamstring, Questionable (10/4).

J. Conner (ARI) – Foot, Out (8/30).

T. Benson (ARI) – Knee, Out (8/25).

H. Long (ARI) – Knee, Questionable (10/4).

Betting Trends

Detroit has hit the moneyline in 50% of its games and covered the -4.5 spread in 25%, while Arizona has hit the moneyline in 25% of its games and covered the +4.5 spread in 25%. HOF's total trend rows for this game also lean toward the over, which lines up with the high 53.5 number the market has set.

Our Pick

Pick: Over 53.5. Detroit's defense ranks 32nd in the league against Rush+Rec Yards, Anytime TDs, and Pass Yards, while Arizona's defense ranks 31st against Anytime TDs and 30th against Pass TDs. With Detroit's offense ranking 3rd in Anytime TDs and both quarterbacks holding strong matchup grades, we like this game to clear a high number.

How We Made Our Lions vs Cardinals NFL Picks and Predictions

Our Lions vs Cardinals NFL picks and predictions are built directly from HOF's sports betting research app rather than gut feel or outside commentary. For every Week 5 matchup, we start with HOF's live point spread, moneyline, and total, then layer in the team grades HOF assigns across offense and defense to see where a real statistical edge exists. From there, we cross-reference HOF's injury report to confirm which players are active, questionable, or out, since a single absence can shift a matchup grade significantly.

We also check HOF's betting trends data — how each team has performed against the spread and the total recently — to see whether the market is lining up with or against the statistical picture. Only after weighing the odds, the matchup grades, the injury report, and the betting trends together do we land on the spread, moneyline, or total pick we publish here. We don't publish a pick without a clear data-backed reason behind it, and we update our numbers as HOF's app updates its own lines and grades throughout the week.

Because lines and injury designations can move between now and kickoff, we recommend checking HOF's app for the latest numbers before placing any wager. A pick that looks strong at one number can lose its edge at another, so the price you can get matters just as much as the side you like.