Brock Purdy has been flying high with the offense, assisted by Christian McCaffrey. Brandon Aiyuk had a stellar Week 1, but was shaken up last week and might miss this matchup with a shoulder injury. Nick Bosa and the defense held the Pittsburgh Steelers to 7 points in the season opener.
To start their season, Daniel Jones and company went six quarters without scoring but came from behind to defeat the Arizona Cardinals last week. Running back Saquon Barkley sprained his ankle in the game and is expected to be out three weeks.
The last time the Giants and 49ers played was in 2020 when San Francisco won 36-9 behind backup quarterback Nick Mullens. Aiyuk had a touchdown on the day.
Will the 49ers be able to continue their dominance?
49ers vs. Giants odds, moneyline, over/under
Spread: 49ers (-10.5)
Moneyline: 49ers (-600); Giants (+425)
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49ers vs. Giants | Ravens vs. Colts | Browns vs. Titans | Lions vs. Falcons | Packers vs. Saints | Jaguars vs. Texans | Dolphins vs. Broncos | Vikings vs. Chargers | Jets vs. Patriots | Commanders vs. Bills | Seahawks vs. Panthers | Cardinals vs. Cowboys | Chiefs vs. Bears | Raiders vs. Steelers | Buccaneers vs. Eagles | Bengals vs. Rams
Lorenzo Reyes: 49ers 27, Giants 13
Short week and a West Coast trip, New York’s offensive line is a mess and the Giants will be without Saquon Barkley. The Niners are explosive pretty much everywhere. Nick Bosa is going to have a field day.
Tyler Dragon: 49ers 28, Giants 10
The 49ers are the best team in the NFL after two weeks. Brock Purdy is managing the game and getting the football to San Francisco’s explosive playmakers. The 49ers’ defense is once again stout with linebacker Fred Warner and defensive end Nick Bosa leading the way. The Giants will be without Saquon Barkley (ankle), which means it’s going to be a long night for New York.
Victoria Hernandez: 49ers 32, Giants 13
The Giants have good momentum after scoring all 31 points in the second half during their come-from-behind win last week but will struggle again without Saquon Barkley. The 49ers are simply the better team all around.
Jordan Mendoza: 49ers 30, Giants 12
The Giants were able to pull off a miraculous comeback in Week 2, but that was against the lowly Arizona Cardinals. Falling behind the 49ers is not something they’ll be able to overcome – especially without Saquon Barkley – as San Francisco cruises to an easy win.
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This article originally appeared on USA TODAY: New York Giants at San Francisco 49ers: Game predictions, picks, odds