49ers vs. Rams on Thursday, September 10 is the first regular-season NFL game ever played in Australia. Kickoff is 8:35 PM ET (5:35 PM PT), which is 10:35 AM local time Friday in Melbourne, at the historic Melbourne Cricket Ground.
The Rams have moved from their opening line of 2.5-point neutral-site favorites to as much as -3.5, with the moneyline sitting at -200, implying a 66.7% win probability. The total is set at 48.5. Bettors have pointed to San Francisco’s unsettled injury picture. The Rams’ offseason additions of Myles Garrett and a returning Aaron Donald are the main drivers behind the line movement.
Expect a competitive, high-scoring affair given both teams’ offensive firepower. The Rams’ healthier roster and continuity on offense should be enough to escape Melbourne with a win. Predicted score: Rams 27, 49ers 23.
San Francisco enters with real question marks. Wide receiver Mike Evans, signed to a three-year deal after 12 seasons in Tampa Bay, has an uncertain Week 1 status after a 2025 season limited to eight games and 368 yards. The 49ers are otherwise considered healthier than last season when Fred Warner and Nick Bosa both suffered season-ending injuries.
For the Rams, veteran defensive tackle Aaron Donald did not practice Monday, though the team described the absence as a planned rest day rather than a new issue. Edge rusher Myles Garrett, acquired via trade, is reported to be making good progress in his integration. Several depth pieces include Terrance Ferguson, Grant Stuard, Keagen Trost, and Justin Dedich. They also have minor situations worth monitoring before kickoff.
This marks the 155th all-time meeting between these NFC West rivals and just the third time they’ve met in Week 1. San Francisco leads the all-time series 79-72-3 and has won six of its last seven road matchups against Los Angeles. They enter on a run of three straight international wins and four straight season-opening victories. The Rams, however, enter as the far more battle-tested team. They’re coming off an NFC Championship Game appearance and a 42-26 win over an injury-riddled 49ers squad in their last meeting back in Week 10 of 2025.
For the Rams, quarterback Matthew Stafford enters as the reigning NFL MVP and is ranked No. 4 on this year’s NFL Top 100 list. He’s throwing to Pro Bowl receiver Puka Nacua. They have a defense now featuring both Donald and Garrett. For San Francisco, Christian McCaffrey played all 17 games last season, rushing for 1,202 yards and 10 touchdowns while adding 924 receiving yards. He remains the offense’s engine alongside quarterback Brock Purdy and tight end George Kittle.
Beyond the standings, this game carries genuine historical weight as the NFL’s first-ever regular-season contest in Australia. For the Rams, a win would validate their status as a preseason Super Bowl favorite. For the 49ers, it’s a chance to prove last season’s injury-plagued finish is behind them. A healthier Kyle Shanahan roster is ready to compete for the NFC West from Week 1.
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