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After the likes of Saquon Barkley, Derrick Henry and even Sam Darnold took the league by storm last year with new teams, many are wondering which old faces in new places will have similar impacts in 2025. The season opener is the first opportunity we'll get to see these player debuts on new teams, but who among them should slot into your Week 1 Fantasy football lineups? Darnold's now onto his fourth team in as many years, while Justin Fields, Geno Smith, Deebo Samuel and DeAndre Hopkins also have new uniforms.

You're likely to spend more time tinkering with your Week 1 Fantasy football picks than any other week, considering there's no in-season data to go off. You can refine your Fantasy football strategy as the year goes on, but Week 1 Fantasy football rankings are almost a must considering roster turnover and depth chart shuffles that are just too much for one to keep track of, including key NFL injuries such as 49ers running back Christian McCaffrey, who is questionable with a calf injury as San Francisco faces Seattle at 4:05 p.m. ET. Before setting your Week 1 Fantasy football lineups, be sure to check out the Week 1 Fantasy football rankings from the proven computer model at SportsLine. 

Bet on every NFL Week 1 game at DraftKings Sportsbook, where new users can target the DraftKings promo code, which offers $300 in bonus bets instantly plus over $200 off NFL Sunday Ticket:

When it comes to ranking players, SportsLine's model beat human experts in Fantasy football for the past several seasons, especially when there were big differences in ranking. Over the course of a season, that could literally be the difference between winning your league or going home emptyhanded.

The same model has a proven track record providing Fantasy football tips, including being ahead of the curve on players like A.J. Brown, Jonathan Taylor, Derrick Henry, Christian McCaffrey, Alvin Kamara, and Jahmyr Gibbs. Anybody who banked on players like those could have made a run at their league title.

Now, the model, which simulates every NFL game 10,000 times, has revealed its Fantasy football rankings for Week 1 of the 2025 NFL season. Head to SportsLine now to see them. 

New users can also bet NFL Week 1 at bet365 and get $300 in bonus bets instantly:

Top Week 1 Fantasy football picks 

One surprise in Week 1: The model is fading Bills running back James Cook, even though he's a two-time Pro Bowler who led the NFL with 16 rushing touchdowns last season. Buffalo will face Baltimore on Sunday night, and the Ravens dominate the trenches like no other team, on both sides of the ball. Baltimore led the NFL in both rushing defense and yards per rush allowed in 2024, a year after it allowed the fewest rushing touchdowns in 2023.

In two games versus Baltimore last season, Cook averaged just 65 scrimmage yards and failed to find the end zone in either. Overall in 2024, Baltimore allowed the fifth-fewest Fantasy points to opposing running backs as Saquon Barkley was the only back to rush for more than 67 yards against the Ravens, counting both the regular season and playoffs. Cook, who had just four touchdowns combined in 20223 and 2023, finished as the RB7 last season but isn't among the top 15 Fantasy running backs for Week 1, per the model's Week 1 Fantasy football projections.

Another curveball: The model is high on Jaguars quarterback Trevor Lawrence, slotting him into the top 10 Fantasy players at his position. Battling multiple injuries, Lawrence played in just nine full games in 2024 but quietly posted the highest QBR and yards per attempt of his career. Last year's Jags saw Brian Thomas Jr. emerge as a top wideout while the team then added Travis Hunter to the receiving core by taking him second overall in the 2025 NFL Draft. With several capable running backs, Lawrence may have as much talent around him as he's ever had as a professional.

The model also recognizes that Jacksonville will take on Carolina on Sunday, and no defense is as giving as the Panthers. They ranked dead last in total yards allowed, points allowed and passing touchdowns given up in 2024. Carolina allowed the second-most Fantasy points to opposing quarterbacks as everyone from Michael Penix Jr. to Marcus Mariota to Cooper Rush had multi-touchdown games against the team. Lawrence is ranked as the QB8 for Week 1 as the model slots him above the likes of Tua Tagovailoa and Jordan Love. For more start/sit Fantasy football advice, be sure to check out the rest of the Week 1 Fantasy football rankings.

How to set Week 1 Fantasy football rankings

The model is also calling for a surprising running back you aren't even thinking about to finish in the top 10 of its Week 1 Fantasy football rankings. This pick could be the difference between winning big and going home with nothing. See the model's entire Week 1 Fantasy football rankings for PPR and standard leagues here.

So who should you start and sit this week, and which surprising running back could lead you to victory? Visit SportsLine now to get Week 1 Fantasy football rankings for every position, plus see which RB is going to come out of nowhere to crack the top 10, all from the model that has outperformed experts big-time.