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

USA - NFL

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

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.

San Francisco 49ers vs Jacksonville Jaguars Form

Table

Teams Pts P W L
4 Jacksonville Jaguars
0.765 17 13 4
7 San Francisco 49ers
0.706 17 12 5

San Francisco 49ers and Jacksonville Jaguars Latest Matches

San Francisco 49ers
San Francisco 49ers Latest matches
L L L W W W
Victories

3/6 (50%)

Defeats

3/6 (50%)

Sep 21, 2025 - NFL

San Francisco 49ers
16 :  15
Arizona Cardinals

Sep 14, 2025 - NFL

New Orleans Saints
21 :  26
San Francisco 49ers

Sep 7, 2025 - NFL

Seattle Seahawks
13 :  17
San Francisco 49ers

Jan 5, 2025 - NFL

Arizona Cardinals
47 :  24
San Francisco 49ers

Dec 30, 2024 - NFL

San Francisco 49ers
34 :  40
Detroit Lions

Dec 22, 2024 - NFL

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

3/6 (50%)

Defeats

3/6 (50%)

Sep 21, 2025 - NFL

San Francisco 49ers
16 :  15
Arizona Cardinals

Dec 30, 2024 - NFL

San Francisco 49ers
34 :  40
Detroit Lions

Dec 12, 2024 - NFL

San Francisco 49ers
6 :  12
Los Angeles Rams

Dec 8, 2024 - NFL

San Francisco 49ers
38 :  13
Chicago Bears

Nov 17, 2024 - NFL

San Francisco 49ers
17 :  20
Seattle Seahawks

Oct 27, 2024 - NFL

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

2/6 (33%)

Defeats

4/6 (67%)

Sep 14, 2025 - NFL

New Orleans Saints
21 :  26
San Francisco 49ers

Sep 7, 2025 - NFL

Seattle Seahawks
13 :  17
San Francisco 49ers

Jan 5, 2025 - NFL

Arizona Cardinals
47 :  24
San Francisco 49ers

Dec 22, 2024 - NFL

Miami Dolphins
29 :  17
San Francisco 49ers

Dec 1, 2024 - NFL

Buffalo Bills
35 :  10
San Francisco 49ers

Nov 24, 2024 - NFL

Green Bay Packers
38 :  10
San Francisco 49ers
Jacksonville Jaguars
Jacksonville Jaguars Latest matches
L W L W L W
Victories

3/6 (50%)

Defeats

3/6 (50%)

Sep 21, 2025 - NFL

Jacksonville Jaguars
17 :  10
Houston Texans

Sep 14, 2025 - NFL

Cincinnati Bengals
31 :  27
Jacksonville Jaguars

Sep 7, 2025 - NFL

Jacksonville Jaguars
26 :  10
Carolina Panthers

Jan 5, 2025 - NFL

Indianapolis Colts
26 :  23
Jacksonville Jaguars

Dec 29, 2024 - NFL

Jacksonville Jaguars
20 :  13
Tennessee Titans

Dec 15, 2024 - NFL

Jacksonville Jaguars
25 :  32
New York Jets
L L L W W W
Victories

3/6 (50%)

Defeats

3/6 (50%)

Sep 21, 2025 - NFL

Jacksonville Jaguars
17 :  10
Houston Texans

Sep 7, 2025 - NFL

Jacksonville Jaguars
26 :  10
Carolina Panthers

Dec 29, 2024 - NFL

Jacksonville Jaguars
20 :  13
Tennessee Titans

Dec 15, 2024 - NFL

Jacksonville Jaguars
25 :  32
New York Jets

Dec 1, 2024 - NFL

Jacksonville Jaguars
20 :  23
Houston Texans

Nov 10, 2024 - NFL

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

1/6 (17%)

Defeats

5/6 (83%)

Sep 14, 2025 - NFL

Cincinnati Bengals
31 :  27
Jacksonville Jaguars

Jan 5, 2025 - NFL

Indianapolis Colts
26 :  23
Jacksonville Jaguars

Dec 8, 2024 - NFL

Tennessee Titans
6 :  10
Jacksonville Jaguars

Nov 17, 2024 - NFL

Detroit Lions
52 :  6
Jacksonville Jaguars

Nov 3, 2024 - NFL

Philadelphia Eagles
28 :  23
Jacksonville Jaguars

Oct 13, 2024 - NFL

Chicago Bears
35 :  16
Jacksonville Jaguars

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

San Francisco 49ers

100 %

Jacksonville Jaguars

0 %

Nov 12, 2023 - NFL

Jacksonville Jaguars
3 :  34
San Francisco 49ers

San Francisco 49ers - Jacksonville Jaguars 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 San Francisco 49ers vs Jacksonville Jaguars 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
$200 offered for betting!

All tips are fully researched and given in good faith, but profits cannot be guaranteed.

San Francisco 49ers vs Jacksonville Jaguars Picks