49ers vs Rams NFL Week 1 TNF Picks

Get up to 1.1% Cash Back — Claim Here

Use Rollcard to fund licensed US sportsbooks, DFS apps, casinos, and prediction markets. Earn cash back on qualifying card spend. New users get double cash back for the first 30 days (standard rates 0.30%–0.55%, doubled up to 1.10%).

Open Rollcard →

The 2026 NFL season is finally upon us. We had a great kickoff to the season Wednesday night with a rematch of last season's Super Bowl from last season between the New England Patriots and the Seattle Seahawks. 

Today we take a trip down under to Australia, where the San Francisco 49ers are taking on the Los Angeles Rams. This divisional battle should be a good one, after wild offseasons for both teams.

The 49ers have had a tumultuous offseason, to say the least. Not only have the 49ers had injuries to their players, like Ricky Pearsall, who will miss the entirety of the 2026 season. But head coach Kyle Shanahan has dealt with injuries to himself after being involved in a car accident where he suffered a concussion. Shanahan looks to have fully recovered from the incident, which is a big plus for this 49ers team.

For the Rams, on the other hand, they have done an unbelievable job this offseason adding to their team after falling a game short of the Super Bowl. They added Trent McDuffie from the Kansas City Chiefs to bolster the defensive secondary. They also brought back old friend Aaron Donald out of retirement to play on the defensive line. Those moves have squarely put the Rams as favorites heading into the season.

All the offseason talk can now stop, as we start to dive into the 2026 season. Throughout the rest of this article, we will break down our three NFL Week 1 TNF picks. Let’s dive right in.

49ers vs Rams TNF Picks

PICK #1: Los Angeles Rams -3.5 over San Francisco 49ers (-110)

PICK #2: Under 48.5 (-110)

PICK #3: Matthew Stafford 2+ Passing Touchdowns (-140)

PICK #1: Rams -3.5 over 49ers (-110)

Even with Kyle Shanahan having an 11-7 record against Sean McVay in his career, we will be taking the Rams to cover the 3.5-point spread. The Rams come into this season with a chip on their shoulder after losing to the Seattle Seahawks in the NFC Championship Game.

This Rams team has so much star power across the board, starting with reigning NFL MVP quarterback Matthew Stafford. He leads a Rams offense that projects to be one of the best offenses in the league once again this season, with weapons like Puka Nacua and Davante Adams on the outside, and a great running back duo with Kyren Williams and Blake Corum in the backfield. 

For us, the 49ers just have too many question marks heading into this game after the wild offseason they had, which we briefly mentioned above. 

They have no Ricky Pearsall. Their star tight end, George Kittle, is trying to come back from a torn achilles in which he suffered late last season and should be on a snap count. They brought in wide receiver Mike Evans from the Tampa Bay Buccaneers, but he has dealt with multiple soft tissue injuries throughout the offseason and he missed a lot of practice time. Plus, the same can be said for their starting running back Christian McCaffrey; he has been in and out of practice with “tightness” after leading the league in touches last season.

For us, with everything that has been going on with the 49ers heading into this game, we feel the most comfortable taking the Rams to cover the -3.5 point spread.

PICK #2: Under 48.5 (-110)

While both play callers and head coaches are considered to be in the NFL, we're expecting this game to stay below the 48.5-point total.

The first thing that stands out to us is the unusual circumstances surrounding this matchup. This is the NFL's first-ever regular-season game in Australia, with the teams traveling all the way to Melbourne for the matchup at the Melbourne Cricket Ground. The 49ers arrived in Australia early to give themselves more time to adjust to the time difference, while the Rams took a much shorter approach to the trip in an effort to maintain their normal routine.

That could make for a slower start offensively, especially with both teams dealing with an entirely different game-day environment than they're accustomed to.

There's also plenty of familiarity between these two NFC West rivals. San Francisco and Los Angeles know each other extremely well, and divisional games between these teams have a tendency to be physical and competitive.

We expect this game to start out slow in the first half, as these teams get their feet wet, so to speak. But the offense should eventually pick up the scoring in the second half, while still staying under that 48.5 game total in theory.

PICK #3: Matthew Stafford 2+ Touchdowns (-140)

Our final pick of the game is Matthew Stafford to throw for at least two touchdowns.

This is probably the easiest player prop to get behind given what Stafford accomplished last season. The veteran quarterback was outstanding in 2025, throwing for 4,707 yards and 46 touchdowns while leading the Rams to a 12-5 regular-season record. He ultimately won the AP NFL MVP award in one of the closest MVP races in league history with Drake Maye.

There are a few reasons why we like this prop. The first of which is that Stafford threw 7 touchdowns combined in the two games against the 49ers, with at least three in each game. Then the chemistry he has with his outstanding weapons is through the roof.

Puka Nacua has had a rough offseason; however, he is coming off an incredible 2025 campaign in which he led the NFL with 129 receptions and finished second with 1,715 receiving yards. He also scored 11 total touchdowns and was voted a unanimous first-team All-Pro.

Then there's Davante Adams, who gives Stafford another elite red-zone target. Adams caught 60 passes for 789 yards and a career-high 14 touchdowns in his first season with Los Angeles. Those 14 receiving touchdowns led the NFL.

At -140, the price isn't particularly cheap, but we believe the matchup justifies it. Plus, Stafford threw a whopping 16 one-yard touchdowns last season, so we know Sean McVay loves to throw the ball down near the goal line. All of those reasons are why we have Matthew Stafford 2+ touchdowns as our favorite prop on the board.