Nov 9, 2025; Santa Clara, California, USA; San Francisco 49ers running back Christian McCaffrey (23) runs the ball against Los Angeles Rams safety Quentin Lake (37) during the second quarter at Levi's Stadium.

Week 1 of Thursday Night Football kicks off tonight, as the San Francisco 49ers and Los Angeles Rams gear up to square off from Melbourne, Australia. The opening TNF matchup of the year features some of the league’s biggest stars including Puka Nacua, Christian McCaffrey and Matthew Stafford. These three players, among many other stars will headline PrizePicks lineups for Thursday’s matchup, with some lines presenting favorable value for bettors.

These are five of my favorite PrizePicks lines for Week 1 of Thursday Night Football:

Kyren Williams has been one of the most consistent backs in the NFL since taking over as the starter in 2023, and has continued to carve out a role in the passing game alongside Stafford. In 2025, Williams racked up career-highs with 36 catches for 281 yards, adding three touchdowns through the air. He’s suiting up in a talented offense alongside one of the top receiving duos in football, but will likely see a few catches as Los Angeles’ offense works to sustain drives against a talented 49ers’ defense.

The Rams’ defense presents a tough matchup for any team, with Myles Garrett set to make his debut on Thursday, and Aaron Donald expected to rejoin the team in a few weeks. Fortunately for San Francisco’s offense, Donald won’t be with the team in Week 1, which could open up greater opportunities for McCaffrey in the run game. Should the passing game struggle, McCaffrey could take on 20-plus carries in the season debut. His 59.5-yard mark presents an immensely favorable line, considering his projected volume as a rusher, and has emerged as one of the game’s more popular picks.

Despite battling a nagging injury, Puka Nacua will suit up for the Rams in Week 1, giving Stafford his favorite target in a big test for the Super Bowl favorites. Nacua racked up a career-high 10 receiving touchdowns in 2025, and will be the team’s premier goal-line threat in the passing game throughout this season. Creative play-calling should free Nacua for a score in the season opener, and his 0.5-touchdown line offers a multiplier to bolster earnings.

Former Defensive Player of the Year Nick Bosa was removed from the team’s injured list ahead of Thursday’s kick-off, and will make his debut in Week 1 coming off a torn ACL in Week 3 of last season. Bosa will likely be limited in his snap-count on Thursday, but presents plenty of reason for optimism in his multiplied 0.5-sack mark, considering his trends of production when he’s healthy. Fortunately for bettors, five-time Pro Bowler is healthy, and will look to make an impact early in year eight.

Demarcus Robsinson is entering his second season in San Francisco, suiting up against his former team and division rivals to start his 10th campaign. Due to a season-ending injury to Ricky Pearsall during training camp, Robinson has been slotted in as WR4 behind Mike Evans, Deebo Samuel and De’Zhaun Stribling. Despite limited volume in 2025, he eclipsed 13 yards in nine of his 14 games a season ago. With Stribling and Evans continuing to build chemistry with Brock Purdy, Robinson’s veteran presence could be leaned on early. The veteran wideout shouldn’t need more than three targets to hit his mark, rounding out our lineup with a favorable line.

Game odds refresh periodically and are subject to change.

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