For the first time, the NFL will play a regular-season game in Australia. The San Francisco 49ers and Los Angeles Rams will make history Thursday night when they kick off their 2026 seasons at the Melbourne Cricket Ground. Kickoff is set for 8:35 p.m. ET (Netflix). Let's analyze NFL odds around the 49ers vs. Rams odds and make our expert NFL picks and predictions for the best bets.
The 49ers come into this game much healthier than they were at the end of last season when they lost just about every key player to injury at some point, from QB Brock Purdy to DE Nick Bosa. Purdy is completely healthy and Bosa is back after tearing his ACL last fall, while TE George Kittle also has a good chance to play following a torn Achilles suffered in January.
Despite being decimated by injuries last year, the 49ers still finished 12-5 and won a playoff game against the Philadelphia Eagles before getting eliminated by the Seattle Seahawks in the divisional round.
The Rams had quite the eventful offseason, adding DE Myles Garrett, CB Trent McDuffie and CB Jaylen Watson. Even DT Aaron Donald came out of his 2-year retirement and returned to the Rams, as he looks to add to his Hall of Fame resume. The Rams went 12-5 last season, too, and like the 49ers, were eliminated by the Seahawks in the playoffs; they lost 31-27 to Seattle in the NFC title game in an unforgettable thriller at Lumen Field. The Rams are the Super Bowl favorites at +500.
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49ers at Rams odds
Provided by BetMGM Sportsbook; access USA TODAY Sports Scores and Sports Betting Odds hub for a full list. Lines last updated Wednesday at 4:23 p.m. ET.
- Moneyline (ML): 49ers +170 (bet $100 to win $170) | Rams -210 (bet $210 to win $100)
- Against the spread (ATS): 49ers +3.5 (-108) | Rams -3.5 (-110)
- Over/Under (O/U): 48.5 (O: -108 | U: -110)
49ers at Rams key injuries
49ers
- DE Nick Bosa (knee) will play
- LB Dre Greenlaw (Achilles) questionable
- TE George Kittle (Achilles) questionable
Rams
- DT Aaron Donald (rest) out
- DE Myles Garrett (knee) will play
- LB Grant Stuard (hamstring) probable
- CB Jaylen Watson (toe) probable
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49ers at Rams picks and predictions
Prediction
Rams 24, 49ers 20
Moneyline
On paper, the Rams are the better team. In fact, they might be the best team in football heading into the season. But betting a moneyline of -210 in the first game of the season isn't always advisable, especially with the game taking place on a neutral field halfway across the globe.
While we're picking the Rams to win, we're going to PASS on the moneyline and instead look at the spread.
Against the spread
The spread is sitting at 3.5, which is a key number for the underdog 49ers. But the Rams are still the better pick against the spread. They now have the cornerbacks to match up against San Francisco's quick passing game, while the pass rush will create negative plays with sacks and potentially tipped passes that lead to interceptions.
McDuffie is the key to it all for the Rams, with his ability to play in the slot and on the outside. Watson matches up extremely well with WR Mike Evans, giving the Rams a corner with the necessary length and physicality go stay in man-to-man coverage with true No. 1 receivers.
BET RAMS -3.5 (-110) to cover the spread and win by at least 4 points.
Over/Under
Neither of these teams played their starters in the preseason, so there could be some rust to knock off in the opener. In Week 1 last season, the Rams only scored 14 points against the Texans, and that was at home. The 49ers, meanwhile, scored 17 in a win over the Seahawks in Week 1 last year.
It's natural for defenses to have a little bit of an advantage early in the year, and with a total of 48.5, that number feels a bit high. BET UNDER 48.5 (-110).
Best prop bet
Rams RB Kyren Williams OVER 53.5 rushing yards (-115)
Including the playoffs last season, there were only 3 games in which Williams didn't have at least 54 yards rushing. One was a low-scoring win over the Ravens, another was a 34-7 blowout against the Buccaneers and the last was the NFC title game loss to the Seahawks.
Even with RB Blake Corum eating into his workload, Williams should get around 15 carries, which will give him a good chance to eclipse this line.
Betting odds calculator
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This article originally appeared on Sportsbook Wire: San Francisco 49ers at LA Rams odds, picks and predictions
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