Jimmy Garoppolo averaged 370.5 passing yards and tossed eight touchdowns against this Arizona secondary last season, so in a game that should be fast-paced, he's a top-12 fantasy QB in Week 1. Jimmy G enters 2020 as an overlooked fantasy QB who's capable of a big season during year two in Kyle Shanahan's system and further removed from ACL surgery.
George Kittle should be busy Sunday with San Francisco's wide receivers banged up, and he gets a Cardinals defense that allowed, by far, the most fantasy points to tight ends in 2019. So he's the top option at his position this week (and season).
San Francisco always runs the risk of a backfield committee. But after scoring 12 touchdowns over his final eight games last season, and getting an updated contract this summer, Raheem Mostert should be considered a top-20 fantasy RB in Week 1 with the 49ers as touchdown home favorites. The addition of Trent Williams has been underrated.
A healthy 49ers defense is a must-start regardless. But there will be easier future opponents than the mobile Kyler Murray and company.
Deebo Samuel and Brandon Aiyuk are safest on fantasy benches while they recover from their injuries, making Jordan Reed a sleeper to score Sunday, as he'll be looked at in the red zone against the TE vulnerable Cardinals.
Kyler Murray, Kenyan Drake and DeAndre Hopkins were all drafted as fantasy starters, but expectations need to be tempered in Week 1 against arguably the league's best defense. SF allowed the fewest yards per attempt (5.9) in the NFL and the third-fewest fantasy points to running backs last season, so this isn't an ideal matchup for Arizona.
Dalton Del Don has been with Yahoo Sports since 2013, covering fantasy football, baseball and basketball. He appears on multiple podcasts each week and currently resides in the Bay Area, where he is an avid fan of the Golden State Warriors and 49ers.