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Come Fan with UsSaturday, June 20, 2026

New York Giants at San Francisco 49ers: betting odds, preview, pick

The Giants are dynamite as underdogs and have dominated the 49ers against the spread in recent years. But many bettors are backing San Francisco and laying a touchdown on the point spread to do so.

If the scores prediction computer is correct, this game will not be the tight, defensive battle many believe it will be.

It’s a rematch of last year’s NFC Championship Game, as the San Francisco 49ers host the New York Giants in Week 6 NFL betting action. San Francisco was a 6.5-point favorite as of Friday at most shops tracked by OddsShark.com.

”Our computer predicts a 40-32 game, but that seems very high,” said Jack Randall. “That result or margin of victory would also result in a 49ers cover, but the computer doesn’t always catch a team’s knack for winning on the road as an underdog, something the New York Giants do better than most NFL teams.”

Indeed, the Giants are 7-1 ATS in their past 8 games as underdog, according to the Week 6 NFL trends list. They are a profitable 5-1-1 ATS in their past 7 games vs the 49ers.

The San Francisco 49ers looked great in wins over Green Bay and Detroit to kick off the season. But since their surprising road loss to Minnesota in Week 3, they’ve taken their game to another level.

San Francisco beat the New York Jets 34-0 on the road two weeks ago and followed that up with a 45-3 blowout win over Buffalo last week.

Now 4-1 SU and ATS, San Francisco is clicking on all cylinders, averaging 29.8 points per game and allowing just 13.6 points per game.

On offense, the New York Giants have played great, averaging 30.4 points per game and scoring over 35 points in three of their five games. Eli Manning is having an outstanding season despite injuries to wide receivers Hakeem Nicks and Ramses Barden (though Nicks may return this week).

But on defense, the Giants have had only one great performance this year in holding Carolina to three points; overall, the unit hasn’t been as dominant as we’ve come to expect under Tom Coughlin.

San Francisco has been on a tear since the beginning of the 2011 season with a 17-5 SU and 15-6-1 ATS record. The 49ers have also been a force at home over the last few years with a 12-2 SU and 12-1-1 ATS record.

Of course, one of those two home losses came to the Giants in the NFC Championship Game last year.

Despite the Giants past successes over San Francisco, we like the 49ers this week. Not only does San Francisco appear to be in top form, but there will also be plenty of pride on the line after the Giants cost the 49ers a Super Bowl berth last year.

It’s a big spread, but San Francisco is more than capable of covering it.

PICK: San Francisco -6.5 (courtesy of PickShark.com)

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