Colts vs Cardinals Predictions Week 16 | NFL Pick of the Day

Last Updated: Dec 25, 2021

Week 16 brings us a Christmas Day matchup between the Cardinals and Colts, two teams in playoff contention that are coming off very different performances. The Cardinals (10-4) needed a win to be the first team in the NFL to clinch a playoff spot, but they lost 30-12 to the now two-win Lions.

What looked to be the biggest issue for the Cardinals was their inability to figure out how to move the ball sans DeAndre Hopkins. The star wideout was ruled out for the remainder of the regular season after tearing his MCL in Week 14.

The Colts (8-6) picked up a huge win at home on Saturday against the Patriots. They’ve won five of their last six games, with their only loss in that span coming against Tampa Bay.

Jonathan Taylor was almost contained by the Patriots for a full game. but that just doesn’t happen to Taylor anymore, as he broke away for a 67-yard touchdown run late in the fourth quarter to cement the victory.

Taylor has an outside shot at being the first running back to win MVP honors since 2012, the year when Adrian Peterson pulled off the feat. Taylor sure has looked like the most valuable player in football since the Colts took the kid gloves off him, as they now regularly give him over 25 touches a game.

We’re in for a great game this weekend, so long as everyone stays healthy (knock on wood). As it stands, both teams have just one player each in health and safety protocols. Let’s look at what these two strong teams have in store for Week 16.

All odds and lines are current as of Thursday, December 23 at 2 PM EST.

Colts vs Cardinals Prediction

It’s easy to want to panic after dropping back-to-back games, including the bad loss to the Lions, but is the panic justified around Arizona?

While the loss of their biggest impact skill player on offense is a cause for concern, the defense could be the bigger issue. Arizona has allowed for Sony Michel and Craig Reynolds to run for 79 and 112 yards against them respectively in their two latest losses.

The Cardinals kept each team in check in terms of yards per carry, but the consistent failure to shut down the run game in any fashion allowed for both the Rams and Lions to score 30 points. Meanwhile, Arizona doesn’t look like a team that can put up 30 points in a game anymore.

James Conner has been a revelation both in the backfield and as a receiver, and the return of Chase Edmonds can only help the offense. Christian Kirk, AJ Green, and Zach Ertz are not an inspiring trio for Kyler Murray to throw to. Serviceable, yes, but not dynamic playmakers anymore.

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The Colts have their playmaker. It’s not Carson Wentz, who threw for just 57 yards in the win last week. Michael Pittman has looked promising, though entirely disappointed last week prior to his ejection.

Trench warfare is what wins Indianapolis games. The Colts have one of the top offensive lines in the league. That power up front along with Taylor in the backfield is an absolute nightmare for any team to deal with.

Missing on the offensive line in Week 15 was Colts center Ryan Kelly, who missed the game due to the passing of his infant daughter. My heart aches for the guy, I can’t imagine how he and his wife feel right now. If he returns, it will be a welcome boost to the offense. If he misses this week’s game, it is 100 percent understandable and will surely be supported by the entire Indianapolis Colts franchise.

Momentum is a curious factor in the NFL. I believe these two teams are playoff bound. However, the Colts have all the momentum in the world right now, while the Cardinals are flailing.

Indianapolis takes this game in the same fashion that they’ve won most of their games recently- sheer dominance by Jonathan Taylor and solid play from their defense and special teams units.

Prediction: Colts 28, Cardinals 24

Kyler Murray, QB, Arizona Cardinals

If the Cardinals are going to end their two-game losing skid against the Colts in Week 16, quarterback Kyler Murray will need some more help from his offensive line and playmakers. (Image: USA TODAY Sports)

Colts vs Cardinals Best Bets

Best Bet: Colts Moneyline (+100) at FOX Bet

Wager: 1.5 Units

I’m taking a stand here. My first article of the season was on the Cardinals @ Titans game in Week 1. I liked Arizona as outright underdog winners on the road due to the improvements it made through free agency and the draft this past offseason.

JJ Watt was one of those important acquisitions. Once again, Watt finds himself on IR after a brutal shoulder injury. There are reports that he could return earlier than expected for a playoff run, though he won’t be playing in Week 16.

I liked Arizona’s draft as well. Linebacker Zaven Collins was their first-round pick, who looked NFL ready. After being named a starter Week 1, he has played sparingly on defense the rest of the season.

I loved Rondale Moore, their second-round pick, as a dynamic threat who can break any play when he has the ball in his hands. Moore has only 511 total yards to date and injured his ankle against the Lions.

Arizona has exceeded expectations to get to 10-4. They are not without their flaws, though.

What will ultimately be their demise is their defense. They’ve allowed a rate of 4.6 yards per carry to opponents this year, the sixth-worst rate in the league. At least Arizona has done well in limiting opponents to 8 rushing touchdowns this year and didn’t allow any in its two most recent losses.

Jonathan Taylor averages 5.6 yards per carry and has 17 rushing touchdowns on the year. He’s scored on the ground 11 games in a row. It simply does not matter what teams throw at him.

So long as the Colts remain underdogs, I like taking them as outright winners. If the spread flips in their favor, then I’d bet it to -1.5 in favor of the Colts.

Best Bet: Over 48.5 Total Points (-110) at FOX Bet

Wager: 1 Unit

I’m wary of the how the Cardinals have looked on offense the past two weeks, but both teams in this matchup are top eight in scoring on the season. They also rate in the top half of the league in plays per game on the year.

These rates are baked into the 48.5 total point line, though there’s still room to hit the Over in what could be a shootout. Indy should set the pace early in this matchup, leaving the Cardinals playing from behind.

The Colts can realistically push for 30 points against a struggling Cardinals defense. The Colts will also have an extra day to rest before the game, as they played on Saturday in Week 15 and this game is on Saturday as well.

Hitting the Over will come down to how well the Cardinals can answer on offense. Both teams are top 10 in fewest points allowed per game on the season, though Arizona is rapidly falling down those ranks.

Kyler Murray was visibly frustrated coming off the field after drives against the Lions stalled out time and time again. With another week of practicing as an offense without DeAndre Hopkins, I think we’ll see signs of life from Arizona.

Murray ran for just three yards against the Lions. As one of the most capable scrambling QBs in the game today, Murray should do much more this week to put the team on his back to move the chains and put points on the board.

Still, the recent injuries and failure to produce for the Cardinals should lead to tempered expectations. I would bet the Over up to 51.5 points, but not any further.

Dane Galloway’s 2021 NFL Betting Record: -10.74 Units

Thank you for reading our NFL Week 16 Colts vs Cardinals Predictions! For more NFL betting content, check out our NFL Week 16 Parlay Picks.


Dane Galloway

Dane Galloway is an NFL analyst at The Game Day from St. Louis, Missouri. He provides NFL betting tips and takes through written content. Dane currently works for Real Time Fantasy Sports and has previously qualified for baseball and basketball DFS live events. He is a lifelong fan of the Reds, Bengals, and Cincinnati Bearcats.

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