Best NFL Picks and Predictions Today (How to Bet 49ers vs. Rams on Thursday Night Football in NFL Week 1)

One of the best matchups in Week 1 of the NFL season gets the standalone treatment on Thursday night, as the Los Angeles Rams and San Francisco 49ers face off in the first-ever NFL game in Australia.

Matthew Stafford and the Rams enter this matchup as the favorite to win the Super Bowl after bringing Aaron Donald (out in Week 1) out of retirement and adding defensive stars Myles Garrett and Trent McDuffie in trades during the offseason.

After an NFC title game appearance in the 2025 season, the Rams are going all-in around their aging core, and Sean McVay certainly can scheme up an elite offense to make them tough to beat.

Meanwhile, San Francisco has sky-high expectations as well in 2026 after making the playoffs – and winning a playoff game – despite a ton of injuries in the 2025 season. Fred Warner, Nick Bosa, George Kittle and Brock Purdy all missed a ton of time during the 2025 season, yet the 49ers’ infrastructure proved to be one of the best in the NFL.

Oddsmakers have set the Rams as favorites in this neutral site game, which features two times trying very different travel plans as they acclimate to the time change in Australia.

All week long, the SI Betting team has examined this matchup to come up with game picks, props and much more. Here’s a look at some of our favorites for the first Thursday Night Football matchup of the season.

Best NFL Picks and Predictions for 49ers vs. Rams in Week 1

Odds via DraftKings Sportsbook

San Francisco 49ers +3.5 (-108) vs. Los Angeles Rams – Iain MacMillan
Davante Adams Anytime TD (+120) – Peter Dewey
Christian McCaffrey OVER 4.5 Receptions (-111) – Peter Dewey
Mike Evans OVER 3.5 Receptions (-130) – Iain MacMillan

San Francisco 49ers +3.5 (-108) vs. Los Angeles Rams – Iain MacMillan

Earlier this week, SI Betting’s senior editor Iain MacMillan shared his favorite bet for this game in his Road to 272 column – where he bets on every NFL game throughout the season:

After the offseason they had, there is more hype behind the Los Angeles Rams this season than I think I've ever seen for a team ahead of the opening kickoff. Maybe they'll end up being as good as advertised, but I think this is a perfect spot to sell high on hype. Until they prove they're as good as the betting market is treating them, I'm going to hang back when it comes to betting on them.

Not only that, but I'm high on the 49ers this season. They had some of the worst injury luck in football last year, but still managed to finish 10th in DVOA. Now, they're relatively healthy, and I expect them to overachieve relative to how the betting market is evaluating them.

Not only that, but this game is in Australia, and the Rams plan to do a "drive-by,” showing up and immediately playing instead of arriving a few days ahead of time to acclimatize. I don't know if that's the smartest strategy for them to utilize.

I'll jump on the 49ers getting more than a field goal in this divisional matchup.

Davante Adams Anytime TD (+120) – Peter Dewey

Rams star Davante Adams was a touchdown machine in the 2025 season, catching 14 touchdown passes in as many regular season games. In the playoffs, Adams scored just once, but 15 scores in 17 games is a pretty great success rate.

The star wideout scored in one of his two games against the 49ers and only had five regular-season games without a score in 2025.

I expect Stafford to continue to air the ball out in 2026, and with Puka Nacua garnering a ton of attention from opposing defenses, it has allowed Adams to become one of the best red zone targets in the league.

Last season, he was targeted 31 times in the red zone (third-most in the NFL) catching 13 passes with 12 of them going for scores.

Christian McCaffrey OVER 4.5 Receptions (-111) – Peter Dewey

Christian McCaffrey had a huge 2025 season, finishing fourth in the league’s MVP voting. CMC should be in line for another huge workload in the 2026 campaign, especially with the 49ers dealing with injuries to Mike Evans and George Kittle heading into Week 1.

McCaffrey had 1,202 rushing yards and 924 receiving yards last season, but I’m looking at his receptions prop on Thursday night.

The star running back dominated the Rams through the air, catching eight of nine targets for 82 yards and a score in their first meeting in 2025 and eight of 10 targets for 66 yards in their second meeting.

Overall, McCaffrey had five or more receptions in 13 of his 17 regular season games in 2025 and both of his postseason appearances. This 49ers offense runs through him more than any other player, and with the Rams featuring an elite pass rush, I wouldn't be shocked if Purdy looks to CMC as his outlet early and often on Thursday night.

Mike Evans OVER 3.5 Receptions (-130) – Iain MacMillan

Not enough has been made of the 49ers acquiring Mike Evans this offseason. Sure, he's not the receiver he once was, but he's still an extremely effective target and will immediately become one of Brock Purdy's most reliable options.

He had 30 receptions for 368 yards in eight games last season. We only need him to haul in four receptions in his 49ers debut for this bet to cash.

Odds refresh periodically and are subject to change.

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