The Arizona Cardinals and San Francisco 49ers will renew their NFC West divisional rivalry this Sunday to kick off their respective 2020 NFL seasons. The following betting preview will find the best Week 1 NFL odds for Cardinals vs. 49ers, as well as give you some trends and NFL picks.

Credit: Chris Victorio/S.F. Examine

Cardinals vs. 49ers Week 1 NFL Odds

  • Opening Lines: FanDuel opened the game as 49ers -7.5; O/U 45
  • Current ATS Line: 49ers -7
  • Over/Under: 48.5
  • Location: Levi’s Stadium, Santa Clara, CA
  • Start Time: 4:25 pm ET
  • Television: FOX
  • Last Meeting: November 17, 2019 – The 49ers beat the Cardinals 36-26 in Santa Clara
  • Attendance: No fans will be allowed to attend Sunday’s game
Odds courtesy of FanDuel Sportsbook

Cardinals vs. 49ers Overview

Year two of the Kliff Kingsbury and Kyler Murray era in the desert begins with even more optimism than the first. While the Cardinals only managed to win five games last season, they added more than a touchdown to their average points per game (22.6) compared to 2018 (14.1). Murray will look to avoid the infamous sophomore slump that plagues so many young quarterbacks.

Offseason trade acquisition DeAndre Hopkins is one way the Cardinals have set Murray up for further success. In what might’ve been the steal of the offseason, Arizona landed the elite receiver and only really parted with David Johnson in the process. Kenyan Drake will assume a workhorse role out of the backfield while Christian Kirk and Larry Fitzgerald round out Murray’s top targets. 2019 was a struggle defensively but drafting Isaiah Simmons 8th overall is a step in the right direction.

For San Francisco, 2020 will be all about staying on top, and the NFL odds expect them to do so. The 49ers surprised many by winning 13 games last year and going all the way to the Super Bowl. In actuality, the foundation for success had been laid in the years prior. A full season of health from Jimmy Garoppolo gave San Francisco the boost it needed. The challenges now are staying on top of arguably the deepest division in the NFL, and ultimately winning a Super Bowl.

Raheem Mostert took the football world by storm down the stretch last season. After inking a contract extension in the offseason, he is poised to be the lead back from the get-go for San Fran. Tight end George Kittle will once again be Garoppolo’s most reliable target, while Deebo Samuel and rookie Brandon Aiyuk will factor in as well. The 49ers’ vaunted defensive front only got stronger with the addition of first-round pick Javon Kinlaw.

Cardinals vs. 49ers Betting Trends

  • Arizona was 2-7 straight up in its last nine games of the 2019 season. 
  • Arizona is 4-0-1 against the spread (ATS) in its last five games against San Francisco. 
  • San Francisco was 6-3 ATS in its last nine games of the 2019 season. 
  • San Francisco was 5-1 straight up in its last six home games of the 2019 season.

Cardinals vs. 49ers 2019 Stats

  • Arizona averaged 22.6 points per game (PPG) during the 2019 season (T-No. 16 in NFL).
  • Arizona surrendered 27.6 PPG during the 2019 season (No. 28 in NFL).
  • San Francisco averaged 29.6 PPG during the 2019 season (No. 3 in NFL).
  • San Francisco surrendered 19.5 PPG during the 2019 season (No. 7 in NFL).

Cardinals vs. 49ers NFL Picks and NFL Odds

Prop Bet

First Half Total: Under 24.5 | -145 (FanDuel Sportsbook)

Odds courtesy of FanDuel Sportsbook

It’s not rare for NFL games to be lower scoring than predicted early in the season. This is because offenses require more practice time and repetitions to get in sync than defenses. With COVID-19 wiping out the entire preseason this year, there’s a real possibility that offenses will be even further behind the eight-ball. Looking at this game, in particular, the Cardinals will be forced to contend with a 49ers defense that ranked second in adjusted efficiency last season (Football Outsiders). Meanwhile, even though Arizona’s defense isn’t overly intimidating, the run-first approach of San Francisco’s offense doesn’t seem likely to change, especially in Week 1. Taking the air out of the ball early on will create a faster-moving first half and less scoring chances for both sides. Playing the first half total under is the way to take advantage.

Cardinals vs. 49ers NFL Pick

The 49ers were eight full wins better than the Cardinals last season, yet only managed to win the two matchups between them by a combined 13 points. Prior to last season, you would have to go all the way back to 2014 to find the last time San Francisco won a game in this series outright. The Cardinals piled up 9 wins in ten games against the Niners from 2014-2018.

All recent games in the series have been relatively close, with only one of the last nine decided by more than 10 points. Logic would tell you that the 49ers are the better team here, and I fully agree that they deserve to be the NFL odds favorite. However, nothing is a given in Week 1, especially coming off the abnormal offseason that was. Look for the Cardinals to stay close in this one. A bet on the even key number of seven should, at worst, result in a push.

Pick: Cardinals +7 | -110 (FanDuel Sportsbook)


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Henry’s passion for sports dates all the way back to childhood and has ultimately led to a full-fledged career as an analyst and content creator. After getting his start penning fantasy football articles, he forrayed into the betting side of the business in early 2019. His love for sports and statistics proved to be an ideal match with the dedicated research and strategy that handicapping requires. Henry currently specializes in betting analysis and picks for college football, college basketball and NASCAR. He counts the NFL, the WNBA, and NBA player props as additional leagues/markets of interest. Henry graduated from SUNY Buffalo in 2021 with a Communication Studies degree and a Psychology minor. A native of the Finger Lakes region in Upstate New York, he and his pup, Harold, have since relocated to Laramie, Wyoming. Thanks to his professional goals within the sports betting industry, there has been a whole lot of steam on the odds for a move to Las Vegas in 2023! Most of Henry’s free time is spent on outdoor adventures, playing chess, snowboarding, or reading a good book. He is also a competitive powerlifter and aspires to qualify for the USAPL Nationals meet within the next 2-3 years.

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