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Arizona Cardinals vs. San Francisco 49ers Prediction and Preview

Arizona Cardinals vs. San Francisco 49ers Prediction and Preview

Arizona Cardinals vs. San Francisco 49ers Prediction and Preview

Two NFC West rivals will look to hit the ground running in 2020 on Sunday as the Arizona Cardinals will take on the defending NFC champion San Francisco 49ers at Levi's Stadium in Santa Clara. The 49ers won both meetings last season against Arizona, beating the Cardinals 28-25 in Glendale on Halloween and then again at home (36-26) on Nov. 17.

San Francisco will be looking to fight off the dreaded Super Bowl hangover. The 49ers are coming off of a 13-3 regular season, NFC championship, and a 31-20 loss in Super Bowl LIV to the Kansas City Chiefs. The offseason caused some personnel losses as expected with Joe Staley's retirement, the departure of Emmanuel Sanders in free agency, and trading DeForest Buckner to Indianapolis during the draft. However, San Francisco's roster is still well-stocked with talent and returns core members like Jimmy Garoppolo, Nick Bosa, Fred Warner, Kwon Alexander, Richard Sherman, and George Kittle so the 49ers enter this season as the favorite to win the NFC West.

Kliff Kingsbury had a tough first few weeks during his first season as head coach in Arizona. The Cardinals got to off a 0-4-1 start but played nearly .500 ball the rest of the way to finish 5-10-1. Kyler Murray will be looking to take another step forward in year two as he showed flashes of his potential to be a great player in the second half of the year and was named NFL Offensive Rookie of the Year. DeAndre Hopkins (104 rec, 1,165 yards, 7 TDs in 2019) was acquired in a trade with the Houston Texans and gives Murray a legitimate No. 1 target. Hopkins will join Larry Fitzgerald and Christian Kirk to round a pretty rock-solid trio of receivers. Safety Budda Baker was rewarded with a four year, $59 million contract extension to make him the highest-paid at his position. Baker along with Chandler Jones will need to continue to elevate the rest of a defense that struggled most of last season.

Arizona at San Francisco

Kickoff: Sunday, Sept. 13 at 4:25 p.m. ET


Spread: 49ers -7

Three Things to Watch

1. 49ers offense

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General manager John Lynch went out and acquired offensive tackle Trent Williams from the Washington Football Team during the draft to replace the retiring Joe Staley. Williams is one of the top left tackles in all of the NFL, when healthy, and he better be ready to go after missing all of last season. That's because he will see his fair share of Chandler Jones, who ranked second in the NFL with 19 sacks in 2019. It will be a huge boost for San Francisco if Williams can handle things against Jones, as that will free up Raheem Mostert and Tevin Coleman and the running game to try and wear down Arizona's defense as the game rolls along. Another byproduct of effectively moving the ball on the ground is that it will set Jimmy Garoppolo and the play-action passing game up nicely. The Cardinals already will have their hands full trying to contain All-Pro tight end George Kittle, who is coming off of back-to-back 1,000-yard seasons.

2. Arizona offense

For the Cardinals, Kenyan Drake will need to set the tone running the football on Sunday. This will not only take some of the aggressiveness out of a stout San Francisco defensive line, it also will inject some valuable confidence into the Arizona offensive line right away. Kyler Murray should end up get his shots early in the passing game and look for him to target new teammate DeAndre Hopkins early and often. In his most recent game against the 49ers, Murray averaged just 4.5 yards per pass attempt (24-for-33), finishing the game with only 150 yards through the air. Finishing drives will be important for Arizona as well after finishing near the bottom of the league (29th) in red zone touchdown percentage (45.28) last season.

3. 49ers defense

This will be a good opening test for a San Francisco defense that ranked fourth in yards and second in points allowed per game last season. Arizona's offense has the potential to be among the most explosive in the league, so taking control of the line of scrimmage will be a great place to start for the 49ers. In two matchups with Murray and the Cardinals last year, San Francisco limited him to a total of 391 passing yards. But this time around, the 49ers' secondary will have to contend with Hopkins in addition to Larry Fitzgerald and Christian Kirk, as well as Drake coming out of the backfield. Savvy veteran Richard Sherman may be given the primary task of clamping down on Hopkins, but the combination of an effective pass rush and sound coverage in the back seven were two key factors in San Francisco boasting the top pass defense in the league in 2019. The 49ers also will need to get the job done against the run, as Arizona averaged six yards per carry in the teams' two matchups last season.

Final Analysis

Murray and Garoppolo are going to flash moments of brilliance in the passing game as they will be able to get the ball to guys in space without too much difficulty. Missed tackles could play a bigger than expected role in this game as the pandemic definitely affected what teams could do hitting-wise in practice. The lack of fans in the stands is an unknown element for everyone including the 49ers. Levi’s Stadium had plenty of energy last season, especially in the playoffs. Hence, it will be intriguing to see how San Francisco responds to that situation and whether or not they can bring their own energy on Sunday. Look for the 49ers to outlast the Cardinals and find a way to cover the spread with a methodical performance on both sides of the football to start the season at 1-0.

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Prediction: 49ers 34 Cardinals 24

— Written by Scott Whittum, who is part of the Athlon Contributor Network. Follow him on Twitter @ScottWhittum.