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Arizona Cardinals 2021 schedule: Toughest stretch, opponent preview, key matchups, predictions and more

There were tangible reasons to justify the Cardinals falling short of the playoffs in 2020. Kyler Murray’s late-season injury was the main reason why Arizona was unable to parlay a 6-3 start into its first playoff berth since 2015. A defense that allowed at least 26 points six times over the season’s last 10 games also contributed to the Cardinals posting a 3-6 record following their Week 8 bye. But all in all, the Cardinals’ 8-8 record was a significant improvement from their 5-10-1 record in coach Kliff Kingsbury’s first season in the desert in 2019.

While some fans may have been inclined to give them a pass last season, that won’t be the case for the Cardinals in 2021, especially after the offseason Cardinals general manager Steve Keim had. On offense, the Cardinals added former Pro Bowlers A.J. GreenJames Conner and Rodney Hudson along with rookie wideout Rondale Moore. Defensively, the Cardinals signed perennial All-Pro pass rusher J.J. Watt as well as former Pro Bowl cornerback (and Super Bowl XLIX hero) Malcolm Butler. Arizona further added to its defense when it spent its first-round pick on Zaven Collins, one of the top-rated linebackers in the draft. 

Despite their roster upgrades, William Hill Sportsbook has the Cardinals’ Over/Under set at 8 games, which would put them below the .500 mark. Below, you can check out my week-by-week breakdown and predictions of every game game on Arizona’s 2021 schedule, including each team’s Over/Under set by William Hill. But first, let’s explore several notable takeaways from Arizona’s schedule as well as pinpointing the toughest part of its upcoming journey. 

Need a quick betting primer on your favorite NFL team for the 2021 season? Here are links to schedule breakdowns for all 32 clubs.

Key schedule observations

  • Arizona’s opponents posted a cumulative .507 winning percentage in 2020, which puts it in a tie with Tennessee for the 13th toughest schedule 
  • Nine games against 2020 playoff teams  
  • Three prime-time games that include a Christmas Day showdown with the Colts 
  • Week 12 bye
  • Nine road games, eight home games 

Toughest stretch

The schedule is relatively consistent, with relatively winnable games often sandwiched between formidable opponents. Two things of note is that the Cardinals will be on the road for four of its first six games. Their toughest stretch takes place after their Week 12 bye. The slate starts with a December game in Chicago, followed by a home game against the Rams. After another road game in Detroit, the Cardinals will play host to the Colts on Christmas Day. The Cardinals will kick off 2022 with a road game against what should be a vastly improved Cowboys team before closing out the regular season against the always tough Seahawks at home.  

Now let’s get to the predictions:

Tennessee Titans 

Week 1 – Sunday, Sept. 12 
Location: Nissan Stadium (Nashville, Tennessee)
Time: 1 p.m. ET 
2020 record: 11-5
Series record: 7-4 (Cardinals lead) 
Opponent win total: O/U 9.5 

The Cardinals’ run defense — 22nd in the league in 2020 — will be immediately tested in 2021 in the form of Derrick Henry, the reigning two-time rushing champion. On offense, Murray should have success against the Titans’ suspect pass defense. It’s a close call, but I’m taking the Titans in a tight-knit, high-scoring affair. 

Prediction: Cardinals lose 31-27

Minnesota Vikings 

Week 2 – Sunday, Sept. 19 
Location: State Farm Stadium (Glendale, Arizona) 
Time: 4:05 p.m. ET 
2020 record: 7-9
Series record: 17-11 (Vikings lead) 
Opponent win total: O/U 8.5

A week after facing Henry, the Cardinals’ defense will again be put up to the test against Dalvin Cook, who finished second in the NFL in rushing last season. Unlike Week 1, I’m taking the Cardinals to win behind the efforts of Murray, who should be able to take advantage of a Vikings defense that finished near the bottom in most defensive categories in 2020. 

Prediction: Cardinals win 30-20 

Jacksonville Jaguars 

Week 3 – Sunday, Sept. 26 
Location: TIAA Bank Field (Jacksonville, Florida)
Time: 1 p.m. ET 
2020 record: 1-15
Series record: 3-2 (Cardinals lead) 
Opponent win total: O/U 6

This one should be fun. The Jaguars, 1-15 last season, should be vastly better under Urban Meyer, who has led a revamping of Jacksonville’s roster that includes the addition of rookie quarterback Trevor Lawrence. This is the type of early-season game against a rookie quarterback where defensive veterans Watt, Butler, Chandler Jones and Budda Baker should thrive. It might be closer than Cardinals fans would want, but the Cardinals should leave Jacksonville with their first road win. 

Prediction: Cardinals win 20-16 

Los Angeles Rams 

First meeting: Week 4 (SoFi Stadium, Inglewood, California) – Sunday, Oct. 3, 4:05 p.m. ET 
Second meeting: Week 14 (Glendale, Arizona) – Sunday, Dec. 13, 8:15 p.m. ET 
2020 record: 10-6 
Series Record: 45-38-2 (Rams lead) 
Opponent win total: O/U 10.5

For a second straight year, the Cardinals dropped both games to Los Angeles in 2020. Whether or not the Cardinals can win at least one of their games against the Rams in 2021 may determine whether or not the Cardinals make the playoffs. Like the Cardinals, the Rams are also expected to be better this season with the addition of former Lions quarterback Matthew Stafford. If healthy, Murray has proven himself capable of having success against the Rams’ talented defense. These matchups will likely come down to how much success Watt and the rest of the Cardinals’ defense can have against Goff and the Rams’ offense. The Cardinals are certainly capable of forcing a series split, but until Kingsbury and Co. prove otherwise, I’m rolling with the Rams in both games. 

Week 4 Prediction: Cardinals lose 38-28
Week 14 Prediction: Cardinals lose 24-20

San Francisco 49ers 

First meeting: Week 5 (State Farm Stadium, Glendale, Arizona) – Sunday, Oct. 10, 4:25 p.m. ET 
Second meeting: Week 9 (Levi’s Stadium, Santa Clara, California) – Sunday, Nov. 7, 4:25 p.m. ET 
2020 record: 6-10
Series Record: 32-27 (49ers lead) 
Opponent win total: O/U 10

Arizona kicked off the 2020 season by beating the then-defending NFC champions. In their Week 17 rematch, the Cardinals dropped a pivotal game to the 49ers after allowing a season-high 227 rushing yards. Rest assured that the 49ers (with a new stable of running backs that includes Wayne Gallman and Trey Sermon) will test the Cardinals’ run defense when they head to State Farm Stadium in Week 5. Along with stopping the 49ers’ running game, a big question in these matchups — along with the Cardinals’ 2021 season in general — will be whether or not the team will get enough from their stable of running backs. The Cardinals, after all, did not bring back Kenyan Drake, the team’s leading rusher each of the previous two seasons. If Arizona can establish its running game in both contests with the 49ers, it will certainly pay dividends and could lead to a series split. 

Week 5 Prediction: Cardinals win 27-24
Week 9 Prediction: Cardinals lose 28-21

Cleveland Browns 

Week 6 – Sunday, Oct. 17
Location: FirstEnergy Stadium (Cleveland) 
Time: 4:05 p.m. ET 
2020 record: 11-5
Series record: 33-15-3 (Browns lead) 
Opponent win total: O/U 10

It’s time to pick an upset. The Browns will likely be favored for this one, and for good reason; they’re deeper and more talented than the Cleveland team that nearly upset the Chiefs in the divisional round of the 2020 playoffs. But the Cardinals’ depth at receiver, along with the new pieces on Arizona’s defense, may be enough to give the Cardinals an upset win. A key here will be whether or not the Cardinals can take advantage of Cleveland’s suspect interior defense. This is where Conner, who had success against the Browns as a member of the Steelers, could shine. 

Prediction: Cardinals win 33-27 

Houston Texans  

Week 7 – Sunday, Oct. 24
Location: State Farm Stadium (Glendale, Arizona)
Time: 4:25 p.m. ET 
2020 record: 4-12
Series record: 2-2
Opponent win total: O/U 4.5

This has the makings of a “trap” game given that it falls between the trip to Cleveland and a home game against the Packers. But if the Cardinals handle their business, this should be one of the most predictable outcomes on Arizona’s schedule. It might not be pretty (Houston will likely try to beat teams by keeping possession and playing bend-but-not-break defense), but a win is a win in the National Football League. 

Prediction: Cardinals win 24-17 

Green Bay Packers 

Week 8 – Thursday, Oct. 28
Location: State Farm Stadium (Glendale, Arizona)
Time: 8:20 p.m. ET 
2020 record: 13-3
Series record: 45-26-4 (Packers lead) 

Similar to Cleveland, Green Bay will likely be favored when it faces the Cardinals, assuming that Aaron Rodgers is still at quarterback. Regardless, I’m taking the Cardinals at home on a short week in front of a national TV audience. This is a game where Watt, Jones and the Cardinals’ pass rush will be key. It is also the ideal spotlight for Murray to reinforce his status as one of the NFL’s top young guns. 

Prediction: Cardinals win 28-24

Carolina Panthers 

Week 10 – Sunday, Nov. 14
Location: State Farm Stadium (Glendale, Arizona)
Time: 4:05 p.m. ET 
2020 record: 5-11
Series record: 13-5 (Panthers lead) 
Opponent win total: O/U 7.5

The Panthers, especially with a healthy Christian McCaffrey, should be better than the five-win outfit they were in 2020. But the Cardinals should win this one, given the quarterback matchup (Murray vs. former Jets quarterback Sam Darnold) and the youth on the Panthers’ defense. 

Prediction: Cardinals win 35-21

Seattle Seahawks

First meeting: Week 11 (Lumen Field, Seattle) – Sunday, Nov. 21, 4:25 p.m. ET 
Second meeting: Week 18 (State Farm Stadium, Glendale, Arizona) – Sunday, Jan. 9, 4:25 p.m. ET 
2020 record: 12-4
Series Record: 22-21-1 (Seahawks lead)  
Opponent win total: O/U 10

Seattle and Arizona split two highly competitive games in 2020, with the home team winning both contests. I’m going with a similar result in 2021, but don’t be surprised if the Cardinals are able to sweep a Seattle team that has several question marks, especially in the secondary. Winner aside, this matchup has turned into must-see viewing, largely because of the quarterback matchup between Murray and Russell Wilson

Week 11 Prediction: Cardinals lose 24-20 
Week 18 Prediction: Cardinals win 27-17

Chicago Bears 

Week 13 – Sunday, Dec. 5
Location: Soldier Field (Chicago)
Time: 1 p.m. ET 
2020 record: 8-8
Series record: 57-28-6 (Bears lead) 
Opponent win total: O/U 7.5 

The Bears’ quarterback situation makes this a tricky game to predict. Regardless of whom is under center for Chicago (barring injury, it will be either veteran Andy Dalton or rookie Justin Fields), Chicago in December is never an easy game, especially for a warm weather team like Arizona. The Cardinals could very well win this game, especially if the Bears’ season is in the dumps by this point. But given the possible weather conditions, along with the fact that the Bears do have one of the league’s more formidable defenses, I’ll pick the Cardinals to fall in the Windy City. 

Prediction: Cardinals lose 20-17

Detroit Lions 

Week 15 – Sunday, Dec. 19
Location: Ford Field (Detroit) 
Time: 1 p.m. ET 
2020 record: 5-11
Series record: 34-28-6 (Lions lead) 
Opponent win total: O/U 5

The Lions, a five-win team in 2020, should be tougher in 2021 with Jared Goff under center and defensive-minded Dan Campbell taking over what was the league’s 32nd-ranked defense in 2020. That being said, the Cardinals should be able to take care of business in the Motor City, especially if the Lions can contain D’Andre Swift while making Goff and the Lions’ offense one-dimensional. 

Prediction: Cardinals win 30-24 

Indianapolis Colts 

Week 16 – Saturday, Dec. 25
Location: State Farm Stadium (Glendale, Arizona) 
Time: 8:15 p.m. ET 
2020 record: 11-5
Series record: 9-8 Cardinals lead 
Opponent win total: O/U 10

Like several other games on their schedule, the opposing team’s unknown quarterback situation makes this a tough game to predict. That being said, I feel confident that Carson Wentz will enjoy some measure of success in Indianapolis, where he will be reunited with Frank Reich (his offensive coordinator in Philadelphia). Given the strength of the Colts’ roster, this should be an exciting Christmas Day game. I’ll take the Cardinals prevailing while improving their postseason odds. 

Prediction: Cardinals win 27-24 

Dallas Cowboys 

Week 17 – Sunday, Jan. 2 
Location: AT&T Stadium (Arlington, Texas)  
Time: 1 p.m. ET 
2020 record: 6-10
Series record: 56-33-1 (Cowboys lead) 
Opponent win total: O/U 9.5

This game may very well come down to the quarterbacks, as the Cardinals’ defense will have to prevent Dak Prescott from having a field day. Arizona’s defense also can’t sleep on Ezekiel Elliott, who is out to regain his place as arguably the NFL’s best running back. Murray and the Cardinals’ offense has enough firepower to keep pace with the Cowboys, but something tells me that Prescott is going to have one of those games. 

Prediction: Cowboys win 34-28 

Cardinals 2021 season projection
Final record: 10-7
Final conference record: 6-6
Final division record: 2-4 




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