Jacksonville Jaguars vs San Francisco 49ers Prediction & Picks - NFL

USA - NFL

Jacksonville Jaguars
9/28/25 16:05
San Francisco 49ers

Prediction:

 

Jacksonville Jaguars +3.5

-118
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 by Matt Lowrimore in NFL Picks

Another one of the games on the Week 4 Sunday NFL slate will see the San Francisco 49ers take on the Jacksonville Jaguars. Let’s take a look at the match statistics and predictions for this game between the 49ers and the Jaguars.

Jacksonville enters this game with a record of 2-1, having beaten the Houston Texans in Week 3 by a score of 17-10. The Jaguars’ offense had a total of 291 yards, while its defense allowed 271 yards. Quarterback Trevor Lawrence threw for 222 yards and one interception, while running back Travis Etienne Jr. led the team in rushing with 56 yards and one touchdown.

As for San Francisco, they enter this game with a record of 3-0, having beaten the Arizona Cardinals in Week 3 by a score of 16-15. The 49ers’ offense had a total of 355 yards, while its defense allowed 260 yards. Quarterback Mac Jones threw for 284 yards, one touchdown, and one interception, while running back Christian McCaffrey led the team in rushing with 52 yards.

Jacksonville Jaguars vs San Francisco 49ers Form

Table

Teams % P W D L
1
San Francisco 49ers
San Francisco 49ers
1 3 3 0 0
14
Jacksonville Jaguars
Jacksonville Jaguars
0.667 3 2 0 1

Jacksonville Jaguars and San Francisco 49ers Latest Matches

Jacksonville Jaguars
Jacksonville Jaguars Latest matches
L W L W L W
Victories

3/6 (50%)

Draw

0/6 (0%)

Defeats

3/6 (50%)

Sep 21, 2025 - NFL

Houston Texans
10 :  17
Jacksonville Jaguars

Sep 14, 2025 - NFL

Jacksonville Jaguars
27 :  31
Cincinnati Bengals

Sep 7, 2025 - NFL

Carolina Panthers
10 :  26
Jacksonville Jaguars

Jan 5, 2025 - NFL

Jacksonville Jaguars
23 :  26
Indianapolis Colts

Dec 29, 2024 - NFL

Tennessee Titans
13 :  20
Jacksonville Jaguars

Dec 22, 2024 - NFL

Jacksonville Jaguars
14 :  19
Las Vegas Raiders
L L L W W W
Victories

3/6 (50%)

Draw

0/6 (0%)

Defeats

3/6 (50%)

Sep 21, 2025 - NFL

Houston Texans
10 :  17
Jacksonville Jaguars

Sep 7, 2025 - NFL

Carolina Panthers
10 :  26
Jacksonville Jaguars

Dec 29, 2024 - NFL

Tennessee Titans
13 :  20
Jacksonville Jaguars

Dec 15, 2024 - NFL

New York Jets
32 :  25
Jacksonville Jaguars

Dec 1, 2024 - NFL

Houston Texans
23 :  20
Jacksonville Jaguars

Nov 10, 2024 - NFL

Minnesota Vikings
12 :  7
Jacksonville Jaguars
L L W L L L
Victories

1/6 (17%)

Draw

0/6 (0%)

Defeats

5/6 (83%)

Sep 14, 2025 - NFL

Jacksonville Jaguars
27 :  31
Cincinnati Bengals

Jan 5, 2025 - NFL

Jacksonville Jaguars
23 :  26
Indianapolis Colts

Dec 22, 2024 - NFL

Jacksonville Jaguars
14 :  19
Las Vegas Raiders

Dec 8, 2024 - NFL

Jacksonville Jaguars
10 :  6
Tennessee Titans

Nov 17, 2024 - NFL

Jacksonville Jaguars
6 :  52
Detroit Lions

Nov 3, 2024 - NFL

Jacksonville Jaguars
23 :  28
Philadelphia Eagles
San Francisco 49ers
San Francisco 49ers Latest matches
L L L W W W
Victories

3/6 (50%)

Draw

0/6 (0%)

Defeats

3/6 (50%)

Sep 21, 2025 - NFL

Arizona Cardinals
15 :  16
San Francisco 49ers

Sep 14, 2025 - NFL

San Francisco 49ers
26 :  21
New Orleans Saints

Sep 7, 2025 - NFL

San Francisco 49ers
17 :  13
Seattle Seahawks

Jan 5, 2025 - NFL

San Francisco 49ers
24 :  47
Arizona Cardinals

Dec 30, 2024 - NFL

Detroit Lions
40 :  34
San Francisco 49ers

Dec 22, 2024 - NFL

San Francisco 49ers
17 :  29
Miami Dolphins
W L W L L W
Victories

3/6 (50%)

Draw

0/6 (0%)

Defeats

3/6 (50%)

Sep 21, 2025 - NFL

Arizona Cardinals
15 :  16
San Francisco 49ers

Dec 30, 2024 - NFL

Detroit Lions
40 :  34
San Francisco 49ers

Dec 12, 2024 - NFL

Los Angeles Rams
12 :  6
San Francisco 49ers

Dec 8, 2024 - NFL

Chicago Bears
13 :  38
San Francisco 49ers

Nov 17, 2024 - NFL

Seattle Seahawks
20 :  17
San Francisco 49ers

Oct 27, 2024 - NFL

Dallas Cowboys
24 :  30
San Francisco 49ers
L L L L W W
Victories

2/6 (33%)

Draw

0/6 (0%)

Defeats

4/6 (67%)

Sep 14, 2025 - NFL

San Francisco 49ers
26 :  21
New Orleans Saints

Sep 7, 2025 - NFL

San Francisco 49ers
17 :  13
Seattle Seahawks

Jan 5, 2025 - NFL

San Francisco 49ers
24 :  47
Arizona Cardinals

Dec 22, 2024 - NFL

San Francisco 49ers
17 :  29
Miami Dolphins

Dec 1, 2024 - NFL

San Francisco 49ers
10 :  35
Buffalo Bills

Nov 24, 2024 - NFL

San Francisco 49ers
10 :  38
Green Bay Packers

Jacksonville Jaguars against San Francisco 49ers : Head to Head (H2H)

Nov 12, 2023 - NFL

San Francisco 49ers
34 :  3
Jacksonville Jaguars

Jacksonville Jaguars - San Francisco 49ers Key Points

  1. Jacksonville is 2-1 ATS this season
  2. Jacksonville is averaging 23.3 points per game this season
  3. San Francisco is 2-1 ATS this season
  4. San Francisco is averaging 19.7 points per game this season

Our Jacksonville Jaguars vs San Francisco 49ers Prediction

San Francisco may be undefeated, but they have not played like an unbeaten team. The 49ers now have two of their quarterbacks on the injury report, that being Brock Purdy and Mac Jones. Both guys are listed as questionable for this game against Jacksonville, so it is unclear who will start for the 49ers.

Additionally, Nick Bosa tore his ACL for the 49ers and is not out for the season, further crippling their defense. Jacksonville, on the other hand, has not looked perfect, but has still found a way to win two of its three games. The Jaguars’ defense has allowed just 17.0 points per game, so given the uncertainty at quarterback for San Francisco, our San Francisco 49ers vs Jacksonville Jaguars prediction is: Jacksonville Jaguars +3.5.

Prediction:

 

Jacksonville Jaguars +3.5

-118
$400+ offered for betting!

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Jacksonville Jaguars vs San Francisco 49ers Picks