49ers vs. Rams prediction, odds: NFL Australia game picks from 10,000 simulations

NFC West contenders open their regular seasons when the San Francisco 49ers battle the Los Angeles Rams in the 2026 NFL Australia Week 1 matchup in Melbourne on Thursday. Both teams tied for second in the division with 12-5 records last year. The Rams fell short to the eventual champion Seattle Seahawks 31-27 in the NFC Championship Game. The Niners also were eliminated by the Seahawks, losing 41-6 in a divisional round matchup. Aaron Donald will not play for the Rams this week as he continues to condition following his return from a two-year retirement. Visit our DraftKings promo code review and get $200 in bonus bets as a new user after $5+ in wagers here:

Kickoff is at 8:35 p.m. ET from Melbourne Cricket Ground. The latest Rams vs. 49ers odds have Los Angeles as 3.5-point favorites, while the over/under for total points scored is 48.5. Before making any 49ers vs. Rams picks, be sure to see the NFL Australia game predictions from SportsLine’s projection model.

The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on betting sites on top-rated NFL picks since its inception. The model enters the 2026 NFL season on a 53-37 run on top-rated picks dating back to 2024. Anybody following its picks at NFL betting sites could have seen strong returns.

Now, the model has zeroed in on 49ers vs. Rams. You can head to SportsLine now to see its picks. Here are several NFL odds and betting lines for Rams vs. 49ers:

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Top 49ers vs. Rams predictions

After 10,000 simulations of 49ers vs. Rams, the model is going Over 48.5 combined points at betting apps. The Rams and their opponents combined to score 49 or more points in 12 of 20 games, including the postseason. Los Angeles averaged a league-best 30.5 points a year ago. San Francisco was 10th in scoring in 2025, averaging 25.7 points.

San Francisco’s Brock Purdy is projected to throw for more than 220 yards and one touchdown. Los Angeles’ Matthew Stafford, meanwhile is projected to throw for over 235 yards and two touchdowns. SportsLine’s model projects 49 combined points between the 49ers and Rams. See which team to back at SportsLine.

How to make 49ers vs. Rams picks

In addition to going Over on the total, the model also says one side of the spread hits nearly 60% of the time. See what it is at SportsLine.

Who wins 49ers vs. Rams, and which side of the spread hits in nearly 60% of simulations? Visit SportsLine now to see which side of the 49ers vs. Rams spread you need to jump, all from the model that is 53-37 on top-rated picks since 2024, and find out.