4:25 p.m. ET | FOX
Matchup rating: 63.2 | Spread: SF -7 (47)
What to watch for: Have the Niners put their Super Bowl disappointment behind them? Is Arizona ready to take the next step to contend after some big offseason additions? These teams played a pair of thrillers last season, with the 49ers winning both by a combined 13 points. If this one looks similar to those, it could portend a season full of heavyweight brawls in the loaded NFC West. -- Nick Wagoner
Bold prediction: DeAndre Hopkins' Cardinals debut will be one to remember. The newest member of the Cardinals' receiving corps will have 150 yards and two touchdowns from quarterback Kyler Murray, showing how far they've come together in a short amount of time and issuing a preview of what's to come. -- Josh Weinfuss
Stat to know: The Cardinals were 1-5 in division games last season, their worst record since 2012, and they lost both of their games against the 49ers. But Arizona hasn't lost three straight to San Francisco since 2012-13. Murray, who became the sixth different QB with 3,500 passing yards and 500 rushing yards in single season in 2019, will have to have a big game to avoid three in a row.
What to know for fantasy: Two of Murray's top five games came against the 49ers last season, and that was without a pass catcher (WR/TE) scoring 16 points in either of those games. Hopkins, though, has 16.5 fantasy points per game for his career and 19.8 over the past three seasons. See Week 1 rankings.
Betting nugget: The Cardinals are 4-0-1 ATS in their last five against the Niners, whereas the Niners are 3-15-2 ATS in their last 20 games as the home favorite. Read more.
Weinfuss' pick: Cardinals 34, 49ers 24
Wagoner's pick: 49ers 31, Cardinals 27
FPI prediction: SF, 70.4% (by an average of 7.8 points)
Matchup must-reads: Cardinals' receiver Hopkins' XXXL hands are 'incredible' ... Can 49ers' Garoppolo get the Kyle Shanahan Year 2 bump? ... Drake will 'stir the drink' for Cardinals offense ... 49ers face questions as they begin pursuit of second straight Super Bowl