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#322 Arizona Cardinals +12 over San Francisco 49ers 3:05 PM CT
San Francisco has won and covered the three meetings since the start of last season in this series even as a big favorite in each game, but none of those games were in Glendale as Arizona’s home game in the series last season was played in Mexico. The 49ers are just 2-6 S/U and 3-5 ATS in the past eight trips to Arizona and Kyler Murray has two S/U wins vs. the 49ers in five tries in his career. The 49ers had just a minimal 395-362 edge in yardage in the Week 4 win started by Josh Dobbs for Arizona, a game that was 21-16 into the 4th quarter before two 49ers touchdowns were added for a misleading final score. Arizona did have a bye week last week ahead of this high-profile game while the 49ers were in Seattle, putting up big numbers for a fifth straight win though that was also a five-point game in the 4th quarter and San Francisco failed against the closing number. San Francisco will likely continue to see its lines swell every week as the one NFL team that has been dominating though many 49ers games have been closer than the final scores this season. Since 2021 NFL home underdogs of 12 or more are 9-3 ATS with five S/U upset wins as the Cardinals may be worth a look particularly with the 49ers looking at a huge Super Bowl preview possibility in next week’s high-profile Christmas Day game with the Ravens.