Cardinals vs. Colts odds, spread, line: 2021 NFL on Christmas picks, Week 16

The Arizona Cardinals are hoping last week’s loss at Detroit was a wake-up call as they take on the Indianapolis Colts in an important interconference matchup on NFL Christmas Day 2021. The Cardinals (10-4), who had the No. 1 seed in the NFC playoff picture just three weeks ago, have lost two straight and now find themselves as the No. 4 seed heading into the weekend. The Colts (8-6), who were all but left for dead in the AFC postseason race, are now back in the thick of things after back-to-back wins over Houston and New England.

Kickoff from State Farm Stadium in Glendale, Ariz., is set for 8:15 p.m. ET. Arizona is a three-point favorite in the latest Cardinals vs. Colts odds from Caesars Sportsbook, while the over-under for total points scored is 48. Before you make any Colts vs. Cardinals bets, make sure to check out the NFL predictions and betting advice from SportsLine’s proven computer model.

The model, which simulates every NFL game 10,000 times, is up over $7,000 for $100 players on top-rated NFL picks since its inception six-plus years ago. The model enters Week 16 of the 2021 season on an incredible 133-96 run on top-rated NFL picks that dates back to the 2017 season.

The model also ranked in the top 10 on NFLPickWatch four of the past five years on straight-up NFL picks and beat more than 94 percent of CBS Sports Football Pick’em players four times during that span. Anyone who has followed it is way up.

Now, the model has simulated Colts vs. Cardinals 10,000 times and just revealed its NFL expert picks and predictions. You can head to SportsLine now to see its picks. Here are several NFL odds and betting trends for Colts vs. Cardinals:

• Colts vs. Cardinals spread: Cardinals -3
• Colts vs. Cardinals over-under: 48 points
• Colts vs. Cardinals money line: Indianapolis +140, Arizona -160
• IND: Colts are 4-0 against the spread in their last four games as road underdogs
• ARI: Cardinals are 9-5 against the spread this season

Why the Cardinals can cover

Running back Chase Edmonds has returned from injured reserve after landing there following an ankle injury last month. Edmonds carried just six times against the Lions, but rushed for 53 yards. He has been a weapon when healthy, including a 12-carry, 120-yard effort against the Rams in October, and has 65 or more yards from scrimmage in three of his four home games in 2021. For the season, he has 82 carries for 483 yards (5.9 average) and one touchdown with three explosive plays of 20 or more yards. He has also converted 23 first downs.

Defensively, linebacker Chandler Jones is looking to make an impact, just as he did in his last meeting with Indianapolis. In the 2017 win over the Colts, Jones had two sacks and a forced fumble, and he looks for his third game in a row against Indianapolis with two or more sacks. Jones, who has 33 tackles, including 27 solo, has registered 9.5 sacks for 71 yards this season with nine tackles for loss. He also has four pass breakups, four forced fumbles and one fumble recovery.

Why the Colts can cover

MVP candidate Jonathan Taylor is proving he is the best running back in the NFL. Taylor leads the league in rushing yards and rushing touchdowns with 1,518 yards and 17 TDs this season. He is also a beast to bring down and is averaging 3.7 yards post contact per rush this season, third-most among NFL running backs with 100 or more rushes. Taylor also lays waste to the right side of the field, averaging 6.2 yards per rush to the right, which is second among qualified NFL backs.

Defensively, linebacker Darius Leonard is coming off a solid week that saw him record an interception, force a fumble and register a tackle for loss. He has a forced fumble and pass breakup in two of his past three games and is the only player in the NFL with three or more forced fumbles (six) and three or more interceptions (three) this season. He is also the only player since 2000 with 15 or more forced fumbles (15) and 10 or more interceptions (10) in his first four seasons in the league.

How to make Colts vs. Cardinals picks

SportsLine’s model is leaning over the total, projecting the teams to combine for 52 points. It also says one side of the spread has all the value. You can only see who to back here.

So who wins Cardinals vs. Colts during the NFL Christmas Day 2021 schedule? And which side of the spread has all the value? Visit SportsLine now to see which side of the Cardinals vs. Colts spread to jump on, all from the advanced model that returned over $7,000 on its NFL picks over the last six seasons, and find out.