Indianapolis Colts vs. Arizona Cardinals Pick – NFL Week 16

The Indianapolis Colts and Arizona Cardinals headline one of two games on Christmas Day in the NFL. The Colts and the Cardinals are in the late game after the Cleveland Browns and Green Bay Packers get the day started at Lambeau Field.

We usually don’t see football on Christmas, the NFL is for Thanksgiving, and the NBA gets Christmas. Unfortunately for the NBA, Christmas falls on Saturday this year, so there are two NFL games.

The Colts and Cardinals is a battle between two teams going in opposite directions. Arizona is coming off a humiliating performance in a 30-12 loss to the Detroit Lions on December 19. The Lions were better on both sides of the ball.

Kyler Murray was held to 257 yards, 1 touchdown, and 1 interception on just 56.1% completions. Including a loss to the LA Rams, 30-23, Murray has passed for 3 interceptions and 1 touchdown in his last two starts.

He’s better than what we’ve seen recently, but he may not be feeling 100% after returning from an ankle injury. Murray isn’t a big guy, and the wear and tear of an NFL season might be getting to him now.

The Cardinals were playing inspired football when Murray was out. They went to the Bay Area and beat the San Francisco 49ers, 31-17.

After a letdown versus the Panthers, 34-10, Colt McCoy did it again, a 23-13 win at Seattle. Murray came back to foil a bad Bears team and then lost their confidence against the Rams.

Meanwhile, the Colts are hot with wins in five of their previous six attempts. They’re coming off a 27-17 W over the New England Patriots a week after embarrassing the Texans, 31-0.

Their only loss since losing to the Titans in overtime on Halloween was a coinflip loss versus the Tampa Bay Buccaneers. That could have gone either way, with the Buccaneers having the ball last and scoring on a long Leonard Fournette touchdown run to go ahead 38-31.

The Colts actually had the ball last, but there was not enough time on the clock to do anything with it. Tampa held with seconds left to hand the Colts a tough loss. That said, a great sign to see the Colts hanging with the Buccaneers.

Head below for our free Colts vs. Cardinals pick on December 25, 2021.

Indianapolis Colts vs. Arizona Cardinals Betting Odds and Team Statistics:

The following odds are courtesy of BetUS:

Teams Spread Moneyline Total
Indianapolis Colts +2.5 (-110) +115 Over 49 (-110)
Arizona Cardinals -2.5 (-110) -135 Under 49 (-110)
Team Data Indianapolis Colts Arizona Cardinals
Overall Record 8-6 10-4
ATS Record 9-5-0 9-5-0
Away/Home Record 4-2 3-3
ATS Away/Home 4-2-0 3-3-0
Points Per Game 28.4 27.0
Points Against Per Game 21.4 20.3
Passing Yards Per Game 204.4 255.1
Rushing Yards Per Game 157.0 121.3

Colts vs. Cardinals Prediction:

The Colts are a hot team going into Week 16. Carson Wentz is playing with a chip on his shoulder with something to prove.

Finding a motivated quarterback to play well was just what the Colts were looking for after Philip Rivers retired. Wentz didn’t feel that he was given a fair shake in Philadelphia and was motivated to go to Indianapolis.

Wentz goes into Saturday night with 23 touchdowns and 6 interceptions on 62.7% completions. He didn’t have to do anything against the Patriots, as Jonathan Taylor ran for a mile.

Taylor went off for 170 yards and a touchdown against a good New England defense. He galloped for 5.9 yards per carry and could be closing in on the MVP award.

On 270 attempts this season, Taylor has run for an incredible 1,518 yards and 17 touchdowns on 5.6 yards per carry. I’m not sure this will go well for the Cardinals this week.

Arizona can be run on, as they’re 18th in the NFL with 112.8 yards against per game. The Lions, who were down their starting running back, gashed the Cardinals last week.

Indianapolis Colts vs. Arizona Cardinals Betting Trends:


  • 8-3 ATS in their previous 11 games
  • 4-0 ATS in their previous four games as a road underdog
  • 4-1 ATS in their previous five games on a Saturday
  • 4-1 ATS in their previous five games versus a team with a winning home record
  • 5-0 ATS in their previous five games on the road


  • 3-8 ATS in their previous 11 games at State Farm Stadium
  • 2-7 ATS in their previous nine games versus a team with a winning record
  • 1-4 ATS in their previous five games as the betting favorite
  • 1-4 ATS in thier previous five games on a Saturday
  • 1-5 ATS in their previous six games versus a team with a winning road record

Lions’ leading rusher, Craig Reynolds, gained 112 yards and 4.3 yards per carry on 26 carries last week. This came after Sony Michel had 70 yards on 4 yards per carry versus the Cardinals. Expect Taylor to run all over the field Saturday night.

The Colts should be the ones to dictate the pace on Christmas in the desert. Kyler Murray doesn’t have it right now. He’s struggling and needs his big target in DeAndre Hopkins back on the field.

Hopkins is done until at least January if not through the playoffs. There was some speculation that the Cards would get desperate and call back Larry Fitzgerald, but he isn’t interested. Murray targeted Christian Kirk and Zach Ertz often last week.

Those are fine weapons for Murray, but these are receivers that should be complementing a star like Hopkins. There isn’t a true No. 1 on the field for the Cardinals without Hopkins. A leader like Fitzgerald in the locker room would help as well.

With Taylor running through brick walls right now and confidence at an all-time high for the Colts, they’re tough to oppose. The Cardinals peaked too early, while the Colts are peaking right now. Please give me the Colts on the road.


Colts vs. Cardinals Pick
Kyle E / Author

Kyle is a veteran of TheSportsGeek and has spent nearly a decade providing accurate sports picks and writeups here. He has been a sports handicapper for 10+ years and started sharing his picks and thoughts in 2011 at TheSportsGeek. His expertise spans across multiple sports, including the NFL, NCAAF, MLB, NHL, and horse racing. Prior to writing for TheSportsGeek, Kyle was a fantasy football expert, who ultimately parlayed it into a successful sports betting career. You can find his picks daily only at TheSportsGeek.

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