The first Thursday Night Football game of the season gives us one of the best rivalries in the NFL and perhaps the most unique travel situation in league history, with the game taking place in Australia.
Kickoff from the Melbourne Cricket Ground is scheduled for 10:35 a.m. local time on Friday, with Los Angeles favored by 3.5 points and the total set at 48.5.
My early look at the game focuses on whether San Francisco can keep another meeting with the Rams close and whether the unusual setting leads to a slower start offensively.
Here are my NFL picks and early 49ers vs. Rams predictions for September 10.
49ers vs Rams predictions
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Early 49ers vs Rams spread pick: 49ers +3.5
The Los Angeles Rams might have the NFL’s most loaded roster, but they’ve struggled to pull away from the San Francisco 49ers in the Sean McVay-Kyle Shanahan era. They’ve faced off 19 times, with Los Angeles going 8-11 straight up and recording only four wins by four or more points. That makes getting the hook with San Francisco especially appealing.
I prefer the 49ers’ approach to the extreme travel, which has potential to be jet lag on steroids (the good kind professional athletes have access to, not the sketchy ones being sold in the locker room at your local YMCA).
San Francisco arrived in Melbourne nearly a full week before kickoff, giving the team time to adjust to the 17-hour difference and prepare locally. The Rams, meanwhile, plan to arrive roughly one day before the game following a 15-hour flight. That’s a major gamble before a physical divisional matchup.
The 49ers are also as healthy as they can realistically expect to be. This could be the best version of San Francisco we see all season, making the 49ers +3.5 my top prediction for the game.
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Early 49ers vs Rams total pick: Under 48.5
I’m also leaning Under 48.5, although it’s not as strong as my position on the spread.
The 49ers’ clearest path to an upset is controlling possession, leaning heavily on Christian McCaffrey and preventing Matthew Stafford from turning this into a shootout.
Los Angeles’ upgraded pass rush should also force San Francisco to rely on shorter throws and sustained drives rather than explosive plays.
Throw in two teams opening the season after dramatically different travel schedules, and some early offensive sloppiness wouldn’t be surprising.
I expect the game to look more like 24-21 than 34-31.
49ers vs Rams odds
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- 49ers vs Rams spread: Rams -3.5
- 49ers vs Rams moneyline: 49ers 36%, Rams 64%
- 49ers vs Rams Over/Under: 48.5
How to watch 49ers vs Rams
- 49ers vs Rams matchup
- Date: Thursday, Sept. 10, 2026, 8:35 p.m. ET
- City: Melbourne, Australia
- Venue: Melbourne Cricket Ground
- TV: Netflix
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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