Giants vs. Rams Prediction, Pick Against the Spread for Monday Night Football

The New York Giants and Los Angeles Rams will clash at 8:15 p.m. ET on Monday, September 21 on ESPN and ABC. The Rams enter Monday’s prime-time contest as a 6.5-point favorite on the spread, via PrizePicks.

The Giants began the John Harbaugh era with an impressive 28-20 win over the Cowboys. Meanwhile, the Rams traveled across the world to Australia and forgot their game in Los Angeles, getting crushed 27-7 by the 49ers.

Below, we'll break down our Giants vs. Rams prediction on the spread for Monday Night Football in NFL Week 2.

All stats are via NFL Next Gen Stats and PFF unless otherwise noted.

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

The New York Tri-State Area is buzzing because both football teams won last week. Before then, the Jets and Giants last won in the same week in Week 6 of the 2022 season.

A takeaway from the Giants in Week 1 is the improvement of QB Jaxson Dart’s passing. Last year, most of his production came from his mobility, and he finished third among QBs in rushing yards (437). However, he struggled in the passing game, finishing 21st in completion rate (63.7%) and 19th in EPA per dropback (0.00). 

In Week 1, he was among the most effective passers, ranking second in completion rate (79.3%) and passer rating (134.2).

One reason for Dart's development may be the improvements on the offensive line. Last season, the Giants ranked 26th in pressure rate (24.8%). Last week, their 15.2% pressure rate was sixth.

It looks like Dart has his two favorite targets. WR Malik Nabers returned to the field for the first time since Week 4 last year after a torn ACL and played well, finishing with 69 yards on 6 catches. The breakout star of the first game, however, was TE Isaiah Likely.

Harbaugh brought Likely in from Baltimore, and he had a coming-out party after spending years in Ravens TE Mark Andrews’ shadow. Likely led the team with 78 receiving yards and 2 TDs vs. the Cowboys.

The Giants’ run game was also impactful. The team accumulated 165 rushing yards, with RB Cam Skattebo averaging 4.5 yards per carry and Dart averaging 4.9.

If the Giants can be productive on the ground and through the air, they could be among the league's best offenses. This may pose trouble for the Rams, who looked dysfunctional in Week 1 under extraordinary circumstances. 

The Rams played the first-ever NFL game in Australia, clashing with an NFC West rival. Each team took a different approach to adjust to the 19-hour time difference. San Francisco arrived in Sydney a week before the game and acclimated, while L.A. left the day before. It looks like the 49ers took the right approach.

QB Matthew Stafford had one of the worst games, as his 155 passing yards were the fourth-lowest as a Ram, along with 0 TDs and 1 INT. RB Kyren Williams wasn’t a notable factor in the matchup with just 41 rushing yards, and WR Puka Nacua, who averaged 107.8 receiving yards per game last season, had just 74.

Defensively, the Rams were under a microscope after their offseason upgrades. They traded for two-time Defensive Player of the Year and single-season sack leader Myles Garrett and former Chiefs CB Trent McDuffie, signed former Chiefs CB Jaylen Watson, and DT Aaron Donald came out of retirement.

The Rams were excited about the Garrett-Donald duo on the defensive line, but the team will have to wait. Garrett has been placed on injured reserve with a lingering knee issue.

There’s another impactful injury to monitor for the Rams. Nacua missed practice on Friday and Saturday, and Rams head coach Sean McVay said he'll be a game-time decision.

Nacua is establishing himself as one of the best wideouts in the league, finishing top four in receiving yards in two of his first three seasons. Losing him could be a big downgrade for the offense.

If Nacua can’t go, the Rams still have WR Davante Adams, who has been the No. 1 man in the past. Last year, Nacua missed Week 7 and in that game, Adams finished with 3 TDs.

The Giants looked great in Week 1, with Dart arguably playing his best game as a pro, while the Rams played one of their worst games in recent memory. Based on how the 2026 Giants look early on, this team could compete with the best in the NFL.

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

The Rams enter Monday’s game as 6.5-point home favorites against the Giants, returning a 1.29x payout if they win outright, via PrizePicks.

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

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

Giants vs. Rams Prediction on Spread for Monday Night Football Week 2: 9/21/26

Here are the key game stats and trends behind our Giants vs. Rams prediction on the spread for Monday, September 21.

• The Giants were fantastic at keeping Dart clean in Week 1, sitting ninth in pressure rate allowed (30.6%). The Rams struggled to get after the QB in Week 1, ranking 27th in pressure rate (27.8%).
• New York did well at establishing the run in Week 1, ranking 10th in EPA per rush (+0.06). Los Angeles struggled against the run, ranking 27th in EPA per rush allowed (+0.19).
• In Week 1, the Giants' CBs allowed 5.4 yards per target in coverage, the team’s lowest mark since Week 10 in 2024. Last week, Stafford was 24th in yards per attempt (6.2).
• The Rams aren't a heavy blitzing defense; residing 30th in Week 1 blitz rate (11.1%) after being 29th (20.9%) in all of 2025. Dart finished second in completion percentage (83.3%), fifth in yards per attempt (9.8), and seventh in passing TDs (2) when not blitzed to open the season.
• The Rams weren't productive outside the tackles last week, as their 4.2 yards per carry were 22nd. The Giants shut down those rushes, placing second in YPC allowed (3.0).

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The Giants can start the season 2-0 for the first time since 2022, when they last made the playoffs. Elsewhere, the Rams try to avoid falling to 0-2 for the first time since 2024, but they could be disadvantaged with Garrett out and Nacua banged up.

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