Jacksonville Jaguars vs San Francisco 49ers Prediction 9/28/2025 Today’s NFL Picks

The Jacksonville Jaguars and San Francisco 49ers meet Sunday in NFL action at Levi’s Stadium. Here’s a Jacksonville Jaguars vs San Francisco 49ers Prediction. This article will include a Jacksonville Jaguars vs San Francisco 49ers Pick.

Jacksonville Jaguars Betting Preview

The Jacksonville Jaguars beat the Texans, lost to the Bengals, and they play the Chiefs next. The Jacksonville Jaguars have split their last 8 games. Trevor Lawrence is completing 55.8 percent of his passes for 671 yards, 4 touchdowns, and 4 interceptions. Brenton Strange and Dyami Brown have combined for 253 receiving yards and 1 touchdown, while Brian Thomas Jr. has 7 receptions.

The Jacksonville Jaguars ground game is averaging 141.7 yards per contest, and Travis Etienne Jr. leads the way with 270 yards and 1 touchdown. Defensively, Jacksonville is allowing 17 points and 292 yards per game. Foyesade Oluokun leads the Jacksonville Jaguars with 23 tackles, Travon Walker has 2 sacks and Jourdan Lewis has 2 interceptions.

San Francisco 49ers Betting Preview

The San Francisco 49ers beat the Saints and Cardinals, and play the Rams next. The San Francisco 49ers have split their last 8 games. Mac Jones is completing 66.3 percent of his passes for 563 yards, 4 touchdowns, and 1 interception. Ricky Pearsall and Christian McCaffrey have combined for 494 receiving yards and 1 touchdown, while Jauan Jennings has 7 receptions.

The San Francisco 49ers ground game is averaging 89.7 yards per contest, and Christian McCaffrey leads the way with 176 yards on 52 carries. Defensively, San Francisco is allowing 16.3 points and 265.7 yards per game. Fred Warner leads the San Francisco 49ers with 30 tackles, Bryce Huff has 2 sacks and Renardo Green has 3 pass deflections.

Jacksonville Jaguars @ San Francisco 49ers Betting Trends: Week 4

Why the San Francisco 49ers will win

• The Jaguars have lost each of their last 11 games against teams that held a winning record.
• The 49ers have won each of their last five games against the Jaguars.
• The Jaguars have failed to cover the spread in each of their last six games against NFC West opponents.
• The 49ers have covered the spread in nine of their last 11 games following a Division win.
• The Jaguars have lost the first quarter in eight of their last nine games against NFC West opponents.
• The 49ers have won the first half in each of their last five home games in September.

Why the Jacksonville Jaguars will win

• The 49ers have lost each of their last two games as favorites against AFC opponents.
• The 49ers have failed to cover the spread in each of their last 10 games at Levi’s Stadium following a win.
• The road team has covered the spread in four of the 49ers’ last five games.
• The 49ers have lost the first half in each of their last three games against AFC opponents.

Total Points Facts

• Seven of the 49ers’ last eight games as favorites following a win have gone UNDER the total points line.
• Each of the Jaguars’ last five games against NFC West opponents have gone UNDER the total points line.

San Francisco 49ers Player Prop Facts

• Christian McCaffrey has scored at least one touchdown in nine of his last 10 appearances at Levi’s Stadium against teams with a winning record.
• Brian Robinson has recorded 33+ rushing yards in eight of his last nine appearances against AFC opponents.
• Kendrick Bourne has recorded 30+ receiving yards in each of his last 10 regular season appearances with the 49ers as favorites.
• Christian McCaffrey has recorded 118+ rushing and receiving yards in seven of his last eight appearances with the 49ers as favorites against AFC opponents.
• Mac Jones has recorded 220+ passing yards in seven of his last eight appearances.
• Mac Jones has recorded 21+ completions in six of his seven previous September appearances with his team as a favorite.
• Heading into Week 4, Nick Bosa ranks T2nd in the league for forced fumbles (2) this season.

Jacksonville Jaguars Player Prop Facts

• Brian Thomas has scored at least one touchdown in each of the Jaguars’ last three games as slight underdogs (<+3.5 points).
• Travis Etienne has recorded 15+ receiving yards in each of the Jaguars’ last six Sunday games as underdogs.
• Travis Etienne has recorded 77+ rushing and receiving yards in nine of his last 12 appearances following a win.
• Trevor Lawrence has recorded 234+ passing yards in seven of his last eight appearances following a win.
• Travis Etienne has recorded 56+ rushing yards in each of the Jaguars’ last three Sunday games.
• Trevor Lawrence has recorded 21+ completions in seven of his last eight appearances following a win.
• Heading into Week 4, Jourdan Lewis ranks 1st in the league for passes defensed (6) this season.

Matchup/League Facts

• Heading into Week 4, the 49ers rank 1st in the NFL in passing yards per game (271.3) this season.
• Heading into Week 4, the 49ers rank T1st in the NFL in average points against in first quarters this season (0.0).
• Heading into Week 4, the Jaguars rank 1st in the NFL in interceptions (7) this season.
• Heading into Week 4, the Jaguars rank T1st in the NFL in turnover differential (+5) this season.

Jacksonville Jaguars vs San Francisco 49ers Prediction

The Jaguars are off to a fine start, and it makes the points worth a look, but we must be reminded that they’ve played the Panthers, Bengals, and Texans. Excuse me if I need to see a bit more from the Jaguars to believe in this start. The 49ers are banged up, but they continue to find ways to win with a quality defense and the best passing attack in the league. This game will tell us a lot more about the Jaguars and just how serious they are. I’m going to lean toward the 49ers and lay the points as they win by a touchdown.