Giants vs. Rams Prediction, Spread, NFL Picks for Monday Night Football

Week 2 of the 2026 NFL season wraps up with an intriguing NFC showdown as the New York Giants travel to SoFi Stadium to take on the Los Angeles Rams on Monday Night Football at 8:15 p.m. ET on ESPN and ABC. L.A. enters as 6.5-point favorites on PrizePicks.

The two teams enter Monday's matchup coming off drastically different Week 1 performances. New York opened the season with an impressive 28-20 victory over the Dallas Cowboys, while Los Angeles struggled in a 27-7 loss to the San Francisco 49ers in Melbourne.

Can the Rams bounce back in their home opener, or will QB Jaxson Dart and the Giants continue their surprising start under new head coach John Harbaugh?

Below, we'll break down our Giants vs. Rams prediction and picks for Monday night's NFL Week 2 game, including the spread, over/under, and player picks for PrizePicks.

Make your Giants vs. Rams picks on PrizePicks now!

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Giants vs. Rams Prediction, Spread, Over/Under for Monday Night Football – September 21

The Giants enter Week 2 with plenty of momentum after controlling the game from start to finish against Dallas. Big Blue dominated possession, keeping the ball for more than 36 minutes.

Dart completed 23 of 29 passes for 230 yards and 3 TDs in the victory while also adding 54 rushing yards on 11 carries. Most importantly, the second-year man avoided turnovers and consistently made smart decisions with his legs, giving New York's offense another dimension.

The Rams are coming off an ugly loss to San Francisco, but the offense has a chance to rebound against a Giants defense that showed plenty of leaks last year and allowed Dallas 165 yards on the ground in Week 1.

QB Matthew Stafford completed just 15 of 25 passes for 155 yards with an INT in Australia. For the most part, he looked like a 38-year-old who had gotten off a 15-hour flight not too long before the game kicked off.

The Rams' defense faces a tough challenge of its own after affording San Francisco 174 rushing yards and 5.8 yards per carry in Week 1. New York just demonstrated that its rushing attack can control a game.

There is a major reinforcement coming, though. DT Aaron Donald is returning from retirement and is expected to make his first NFL appearance in nearly 1,000 days. Los Angeles will need him to help stabilize a defensive front that is already without DE Myles Garrett, who was placed on injured reserve.

The biggest offensive question for Los Angeles is WR Puka Nacua. The star missed Friday and Saturday's practices with a hip injury and is listed as questionable. Nacua caught 5 passes for 74 yards in Week 1 after leading the NFL with 129 receptions and logging 1,715 yards and 10 TDs last season.

Giants vs. Rams Spread, Over/Under – Monday, September 21

Los Angeles enters Monday night's game as a 6.5-point home favorite against New York, via PrizePicks, returning a 1.29x payout with an outright win.

Here are the full payouts for Giants vs. Rams on PrizePicks.

Make your Giants vs. Rams prediction on the spread or over/under on PrizePicks.

Team Picks data is live at the time of writing and is subject to change.

Giants vs. Rams Prediction on Spread for Monday Night Football – 9/21/26

Here are the key stats and predictions behind our Giants vs. Rams prediction on the spread for Monday night.

• The Rams have the biggest mismatch: their offense against the Giants' defense. Sharp Football Analysis currently ranks the Rams No. 5 in overall offensive efficiency and the Giants No. 25 in overall defensive efficiency.
• Los Angeles owned the seventh-most rushing yards in the league last year (2,152), while New York ranked dead last in EPA/rush allowed (0.109, via RBSDM).
• The Rams' offensive line also provides a major reason to expect a better performance. L.A. allows a 22.2% pressure rate, while the Giants' defensive line generated pressure on 29.7% of opponent dropbacks last week, one of the lowest marks in the league.
• Los Angeles used 13 personnel on 36.8% of its offensive snaps in Week 1, the highest clip in the NFL. Stafford completed all 5 of his passes from that personnel grouping for 96 yards, averaging an absurd 19.2 yards per attempt.
• That heavy personnel can also create a favorable environment for the run game, as it puts three TEs on the field and increases overall blocking power.
• The Giants' offense gave up pressure on 29.4% of dropbacks in Week 1, and even this Garrett-less Rams front could still be strong in Week 2.
• Los Angeles returns to SoFi Stadium for its home opener with 11 days between games, giving head coach Sean McVay and his staff more time to prepare.

Lock in your Giants vs. Rams prediction on PrizePicks before Monday night's NFL game.

Giants vs. Rams Picks, Player Stats for PrizePicks: 9/21/26

Here are the top Giants vs. Rams picks to target on Monday, September 21, including PrizePicks NFL projections for QBs Matthew Stafford and Jaxson Dart.

Rams QB Matthew Stafford vs. Giants: 238.5 Pass Yards

• This projection just seems far too low for Stafford, who averaged 276.9 passing yards per game in 2025.
• The Rams ranked among the NFL's best passing offenses in 2025, generating +0.22 EPA/play, while Stafford finished the season with one of the league's highest passing grades.
• The Giants’ pass defense isn’t anything to fear either. Last year, it ranked 16th in EPA/play ceded (-0.02).
• Even without Nacua, the Rams would still have an elite WR in Davante Adams. The veteran wideout led the sport with 12 red-zone receiving TDs in 2025, and a reliance on 13 personnel again could likely still keep him on the field.

Add Matthew Stafford + Rams to cover the spread to your PrizePicks lineup now.

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Giants QB Jaxson Dart vs. Rams: 33.5 Rush Yards

• Dart immediately established himself as a legitimate rushing threat under Harbaugh and OC Matt Nagy in Week 1, gaining 54 yards on 11 carries against Dallas.
• The Rams ranked dead last in ERA/rush (0.18) to start the new campaign.
• New York's offensive success in Week 1 could force the Rams to dedicate extra resources to RB Cam Skattebo and the Giants' backs rather than exclusively spying on Dart.
• The Rams have a strong secondary, ranking 11th in EPA/pass (-0.11) in 2025; this could actually encourage Dart to scramble when his initial reads aren't available.
• Game script isn't a concern for this matchup. If New York trails, that would force Dart into more dropbacks, which increases the amount of scrambling opportunities.

Add Jaxson Dart + Giants to win to your PrizePicks lineup now.

Make Giants vs. Rams Picks on PrizePicks

Monday night's matchup provides an intriguing contrast between a Giants team riding high after a statement victory over Dallas and a Rams squad desperate to erase the memory of its Week 1 disaster.

Don't wait until kickoff — make your Giants vs. Rams picks on PrizePicks. There's a wide variety of player stat projections on the board, so you can make predictions on yards, touchdowns, and more! Just pick your players, predict More or Less on their stats, and cash in on your predictions if you're right.

With Team Picks, you can make predictions on game winners, spreads, and over/unders, now available on PrizePicks.

Keep it here with the Playbook for continued NFL picks, predictions, futures, and more as we jump into 2026.