49ers vs Seahawks Prediction 9/7/25 NFL Picks Today

In this article, we will formulate a 49ers vs Seahawks Prediction for this NFL Week 1 game on Sunday, September 7^th at the Lumen Field. Let’s take a look at the prediction for this NFL matchup.

Seattle Seahawks Preview

Seattle finished the preseason with a 1-1-1 record. They had a 23-23 tie at home against the Raiders in the first game, then won the 49ers at home by 33-16, and ended up losing in Green Bay by 7-20. Offensively, Seattle finished the preseason averaging 21 points per game, while allowing 19.7 points per game defensively. The Seahawks averaged 189.3 rushing yards and 176.7 passing yards per game. They allowed 102.7 rushing yards per game and 148.7 passing yards per game.

Drew Lock led the Seahawks in the preseason with 30/47 completed passes and 276 total passing yards. He also had 2 touchdowns and 2 interceptions. Jalen Milroe had 16/29 passes for 170 passing yards and 2 touchdowns, while Sam Darnold added 9/13 passes for 73 passing yards. George Holani led the team in rushing yards, with 110 and 1 touchdown, while Cody White had a team-high 8 caught passes for 69 receiving yards.

Defensively, Drake Thomas had a team-high 14 total tackles, while D’Anthony Bell had a team-high 1 sacks, and Nehemiah Pritchett had a team-high 1 interception.

San Francisco 49ers Preview

San Francisco finished the preseason with a 2-1 record. They lost in the opener at home by the Broncos, 9-30, then won the Raiders on the road by 22-19 and the Chargers at home by 30-23. Offensively, San Francisco finished the preseason averaging 20.3 points per game, while allowing 24 points per game defensively. The 49ers averaged 81 rushing yards and 132 passing yards per game. They allowed 104 rushing yards per game and 216 passing yards per game.

Joshua Dobbs led the 49ers in the preseason with 33/53 completed passes and 383 total passing yards. He also had 3 touchdowns and 1 interception. Brock Purdy had 17/25 passes for 193 passing yards and 1 touchdown, while Joshua Johnson added 18/28 passes for 180 passing yards and 1 touchdown. Jordan Mason led the team in rushing yards, with 97 and 1 touchdown, while Ricky Pearsall had a team-high 10 caught passes for 126 receiving yards, and had 1 touchdown.

Defensively, Malik Mustapha had a team-high 14 total tackles, while Shilique Calhoun had a team-high 2 total sacks, and Chase Lucas had a team-high 1 interception.

Why the Seattle Seahawks will win

• The 49ers have lost 12 of their last 13 Sunday games at Lumen Field.
• The Seahawks have won each of their last three games as underdogs against NFC West opponents.
• The 49ers have failed to cover the spread in eight of their last nine games.
• The underdogs have covered the spread in six of the Seahawks’ last seven Week 1 games.
• The Seahawks have won the first quarter in each of their last three home openers as underdogs.
• The Seahawks have scored the first touchdown in six of their last seven Week 1 games.
• The Seahawks have won the first half in each of their last six Week 1 home games against NFC opponents.

Why the San Francisco 49ers will win

• The road team has won 12 of the Seahawks’ last 13 games.
• The Seahawks have lost each of their last four season openers against NFC West opponents.
• The Seahawks have failed to cover the spread in each of their last four games.
• The road team has covered the spread in each of the last four games between the 49ers and Seahawks.
• The favorites have won the first half in each of the 49ers’ last eight Week 1 games.
• The 49ers have won the first quarter in each of their last eight games as favorites against NFC opponents.
• The 49ers have scored the first touchdown in each of their last seven games against the Seahawks.

Total Points Facts

• Each of the 49ers’ last six road games against NFC West opponents have gone OVER the total points line.
• Seven of the Seahawks’ last eight home openers against NFC opponents have gone UNDER the total points line.
• Four of the last five Sunday games at Lumen Field have gone UNDER the total points line.

Matchup/League Facts

• Seahawks – two different players recorded 100+ rushing yards in a game last season – equal-most in the NFL.
• The Seahawks played in the NFL’s lowest scoring game last season (6 – 3 vs Chicago on December 26, 2024).
• 49ers – four different players recorded 70+ rushing yards in a game last season – equal-most in the NFL.
• 49ers – three different players recorded 80+ rushing yards in a game last season – equal-most in the NFL.

49ers vs Seahawks Prediction

Both teams were tied 1-1 wins last season, with each one winning on the road. The Seahawks won in San Francisco by 20-17 and the 49ers in Seattle by 36-24. The 49ers are 6-1 in their last 7 head-to-head meetings against the Seahawks, and have won their last three visits in Seattle. They are also 5-2 against the spread in their last seven meetings, and over is 3-1-1 in their last 5 meetings.

In this 49ers vs Seahawks Prediction, the 49ers are coming as -2.5-point road favorites. It is always a risk to pick a road team to win a season opener, but I like my chances with the 49ers in this one. Their only loss in the preseason was by the red-hot Broncos who went undefeated in the preseason, and they have also been dominating the Seahawks in recent years, and haven’t lost in Seattle since 2021, including a 36-24 win last season. Ultimately, though, San Francisco’s depth, talent, and coaching edge will decide the outcome. Take the San Francisco 49ers and lay the points on the road.