One of the best games of the week features the Indianapolis Colts and Arizona Cardinals on Christmas night. Both of these two teams are currently in the playoffs in their respective conferences, but they need wins to keep their current seeding.

The Colts are coming off a huge win against the Patriots in which Jonathan Taylor ran for 170 yards. They are finally starting to click on both sides of the ball as they’ve now won seven of their last nine games. Meanwhile, the Cardinals and the Arizona sports betting fans who back them are on a losing streak for the first time this season. Arizona has dropped games to the Rams and Lions in back-to-back weeks and is suddenly in danger of not winning the NFC West.

To get you ready for this AFC-NFC matchup, here is everything you need to know from an NFL betting perspective along with our NFL picks going into Week 16.

Check out the latest Cardinals vs Colts odds, betting lines, injury report and more.

Colts vs. Cardinals Matchups

Colts WR Michael Pittman vs. Cardinals CB Marco Wilson: Pittman is the most dangerous receiver for the Colts and should be able to find success against the young secondary of the Cardinals.

Cardinals WR A.J. Green vs. Colts CB Xavier Rhodes: With DeAndre Hopkins out for the season, Green is now the de facto No. 1 receiver. He should see double-digit targets in this game on the outside for Arizona.

Cardinals RT Kelvin Beachum vs. Colts DE Kwity Paye: Paye has recorded a QB hit in three-straight games and is the team’s best EDGE rusher. He should have a big day against Beachum on the right side.

RELATED: NFL Week 16 Odds & Betting Lines For All Games

Colts vs. Cardinals Stats

28.4: The Colts have the No. 3 scoring offense in the NFL, averaging 28.4 points per game.

94: The Cardinals have a point differential of +94 this season, sixth-best in the NFL.

5-0: The Colts are 5-0 ATS in their last five road games.

3-8: The Cardinals are 3-8 ATS in their last 11 home games, dating back to 2020.

20.3: The Cardinals have the fifth-best scoring defense in the NFL, allowing only 20.3 points per game.

Colts vs. Cardinals Moneyline

This is a really tough game to pick as the Cardinals are probably the better team, but the Colts are certainly playing better. However, it’s still hard to trust Carson Wentz in a big game on the road. Kyler Murray has not played particularly well either, but it’s easier to trust him and the rest of the Arizona offense if they get behind in this game.

Considering this game is in Arizona and on a short week, take the Cardinals (-125) on DraftKings in this prime-time contest on Saturday night.

Bet $5, Get $150 Instantly

Tap for Promo Activated! Visit site

Used 36 Times Today

21+ and present in most states. (18+ DC/KY/NH/WY). Void in IA/KS/KY/LA/MD/MI/NJ/NY/TN/VA/VT/ONT. Eligibility restrictions apply. On behalf of Boot Hill Casino & Resort (KS). 1 per new customer. Min. $5 deposit. Min. $5 bet. Max. $150 issued as non-withdrawable Bonus Bets that expire in 7 days (168 hours). Stake removed from payout. Terms: dkng.co/bball. Ends 1/5/25 at 11:59 PM ET. Sponsored by DraftKings. GAMBLING PROBLEM? CALL 1-800-GAMBLER, (800) 327-5050 or visit gamblinghelplinema.org (MA). Call 877-8-HOPENY/text HOPENY (467369) (NY). Please Gamble Responsibly. 888-789-7777/visit ccpg.org (CT), or visit www.mdgamblinghelp.org (MD).

Colts vs. Cardinals Point Spread

Yes, the Cardinals are struggling. But it’s still hard to believe that they are less than a 3-point favorite at home on most betting sites. That means that most sportsbooks believe that on a neutral field, the Colts are a better football team.

That might be true, especially with DeAndre Hopkins and J.J. Watt both out for the season. Still, it’s hard to bet on the Colts in this situation with Wentz not playing particularly well in the last month of the season. Considering how low this point spread is, take the Cardinals -1.5 and look for them to get a close win in this Week 16 matchup.

New users at BetMGM can get a risk-free first bet worth up to $1,000 to use on the NFL this weekend. Just check out our BetMGM bonus code page for more information or hit 'Bet Now' to get started.

Up to $1,500 in Bonus Bets if Your First Bet Loses Promo Code: BOOKIES

Tap for Promo Activated! Visit site

Used 63 Times Today

Bonus Bets Expire in 7 Days. One New Customer Offer Only. Must be 21+ to participate & present in OH. In partnership with MGM Northfield Park. Gambling problem? Call 1-800-GAMBLER. Visit BetMGM.com for T&Cs. US promotional offers not available in NY, NV, or Puerto Rico.

Colts vs. Cardinals Totals

There are not a lot of high NFL spreads or point totals this week. That is due to a lot of games having playoff implications and potentially bad weather in a few matchups. However, weather won’t play a factor here as the Cardinals play in a dome.

That is why this point total sits at 50, which is the highest of Week 16. While both offenses rank inside the top-10 in points per game, this game has all the makings of a low-scoring contest in which both teams lean on their run games. Take the Under 50 (-110) and expect a 24-21 type of game between the Colts and the Cardinals.

$1,000 First Bet on Caesars Promo Code: BOOKIES1000

Tap for Promo Activated! Visit site

Used 18 Times Today

Must be 21+ to participate. T&Cs apply.