The Giants stormed back from a 21-point deficit Sunday against the Cardinals to avoid an 0–2 start. Their reward is facing the 49ers on the road four days later without Saquon Barkley.

San Francisco, which has the second-best point differential in the NFL (+30), is a 10.5-point home favorite over New York at Levi's Stadium on Thursday Night Football. The total is set at 45.5 points, which gives the Giants an implied total of 17 points.

Daniel Jones is 0–1 in his career against the 49ers, who left MetLife Stadium with a 36–9 victory when these teams last met in 2020. Barkley missed that game as well.

The all-time series between San Francisco and New York is tied 21–21.

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Giants vs. 49ers Odds and Game Info

Moneyline: Giants (+420) | 49ers (-568)

Spread: NYG +10.5 (-110) | SF -10.5 (-110)

Total: 44.5 — Over (-118) | Under (-110)

Game Info: Thursday, Sep. 21, 8:15 p.m. ET | Prime Video

Giants vs. 49ers Best Bet: 49ers Over 27.5 Points (-110)

The Giants were outscored 60–0 through the first six quarters of the season. Following a 40–0 blowout to the Cowboys in Week 1, Brian Daboll’s squad trailed 20–0 at halftime Sunday in Arizona. New York responded with a monster second half, led by Daniel Jones’s three-touchdown effort, and went on to win 31-28. Still, no team has a worse point differential (-37) or more points allowed (68).

Barkley (ankle) is expected to miss three weeks. He was a key part of the comeback effort as he punched in a touchdown from one yard out, scored on a nine-yard catch from Jones and tallied 92 total yards. Matt Breida, who began his career with the 49ers, took over for Barkley in the backfield after he exited the game.

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Rookie receiver Jalin Hyatt led the team in receiving with 89 yards on two grabs and Darren Waller racked up 76 yards on six catches. Jones’ 321 passing yards were more than triple his output against Dallas.

Turnovers and sacks were not nearly as big an issue for the Giants against the Cardinals as they were in the Cowboys game. But against a top-tier defense like San Francisco, those issues could rear their head again, especially with tackle Andrew Thomas (hamstring) and guard Ben Bredeson (concussion) questionable for Thursday’s contest.

The 49ers’ defense was dominant in the team’s 30–7 Week 1 win over the Steelers. The unit intercepted Kenny Pickett twice and sacked him five times. The Rams had more success on offense in a 30-23 loss to their division rival, but San Francisco still picked off Matthew Stafford twice and pressured him throughout the game.

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The Brock Purdy-led offense has been one of the league’s best so far. Only two teams average more points per game than the Niners and Christian McCaffrey leads the NFL in rushing by a wide margin. Brandon Aiyuk shined against Pittsburgh with over 100 yards receiving and two touchdown catches and Deebo Samuel had a big day against Los Angeles as he went over 100 total yards and ran in a score. Aiyuk (shoulder) is currently questionable.

George Kittle’s receiving stats have been pedestrian so far by his standards and McCaffrey’s involvement as a receiver has been limited, which is just further evidence this offense can still go up a level.

The 49ers have scored 30 or more points in all but one of Purdy’s seven regular-season starts. The fact they’re at home against a Giants defense that just surrendered a big offensive output to the Cardinals is even more encouraging for San Francisco’s team over. New York is the only team in the NFL without a sack and is one of five without a takeaway. Purdy should be primed for a big day at Levi’s Stadium, where San Francisco went 8–1 last season.