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Cardinals vs. 49ers Odds & Betting Predictions - September 21, 2025

Cardinals at 49ers

8:25 pm • FOX
Stream Live on SiriusXM - Free 3 Month Offer

Arizona Cardinals

2-0
@

San Francisco 49ers

2-0

Cardinals at 49ers Odds

Spread, Total, Moneyline

MatchupOpenSpreadTotalMoneyline
Cardinals
2-0
+3.5
+1.5-110
o43.5-110
+102
49ers
2-0
u47.5
-1.5-110
u43.5-110
-122
location pinSunday 8:25 p.m.
September 21, 2025
Levi's StadiumSanta Clara
thermometer image79°Fahrenheit
rain image0%Rain
wind image4Wind
Cardinals vs. 49ers Expert Picks
Chris Raybon
Chris Raybon
Last 30d: 14-11-0 (+14.3u)
SF +1.5-115
1.15u
▶️ ARI could be w/o all 3 starting CBs ▶️ ARI getting outgained by 54 yards per game (316-276 by NO, 352-293 by CAR) despite 2-0 record, +12 Pt Diff ▶️ SF 2-0, +9 but outgaining opponents by 96 yards per game (SEA 384-230, NO 344-307) ▶️ Mac outplayed Kyler vs common opponent NO: Kyler 2 TD, 130 net pass yds on 34 DB (3.8 NYA), Jones 3 TD, 267 net yd on 42 DB (6.4 NYA) ▶️ Week 3 home dogs coming off 2-0 SU start are 13-5 (72%) ATS since ‘06, covering by 6.9 PPG — including 10-4, +7.5 ATS diff vs. 2-0 SU opponent.
Brandon Kravitz
Brandon Kravitz
Last 30d: 22-29-0 (-7.0u)
SF +100
1u
FTN Fantasy
FTN Fantasy
Last 30d: 63-94-0 (-36.6u)
SF +100
1u
SF +1-110
1u
Top Shelf Action 🥃
Top Shelf Action 🥃
Last 30d: 129-150-2 (-28.7u)
Under 43.5-110
1u

Cardinals vs. 49ers Previews & Analysis

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Cardinals vs. 49ers Props

Prop Projections

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Prop Odds Comparison

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Line Movement Tracker

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Cardinals vs. 49ers Public Betting Percentages

Away Logo

Cardinals

Public

Home Logo

49ers

49%

Bets%

51%

Money%

NFL Public Betting Right Arrow

Betting Trends

  • 49ers are 2-0 in their last 5 games.
  • 49ers are 2-0 in their last 5 games against the spread
  • 49ers are 2-0 in their road games against the spread
  • The totals have gone OVER in 1 of 49ers' last 2 games

Matchup History

Against the Spread (ATS) History

overallhomeawayfavoriteunderdog
49ers		2-0N/A2-02-0N/A
Cardinals		1-10-11-01-1N/A

Over/Under History

overallhome o/uaway o/ufavorite o/uunderdog o/u
49ers		1-1N/A1-11-1N/A
Cardinals		1-11-00-11-1N/A

Straight-Up (ML) History

overallhomeawayfavoriteunderdog
49ers		2-0N/AN/A2-0N/A
Cardinals		2-0N/AN/A2-0N/A

Last 5 Matchups

dateopponentscorespreadover/undermoneyline
Sep 14th@NOW 26-21-3 WO 40.5SF -160
Sep 7th@SEAW 17-13-2.5 WU 43.5SF -132
Aug 24thLACW 30-23+2.5 WO 35.5SF +125
Aug 16th@LVW 22-19+4.5 WO 40.5SF +180
Aug 10thDENL 9-30+6.5 LO 38.5DEN +240

49ers vs. Cardinals Injury Updates

49ers Injuries

  • Kyle Juszczyk
    FB

    Juszczyk is doubtful with concussion

    Doubtful

  • Demarcus Robinson
    WR

    Robinson is out with suspension

    Out

  • George Kittle
    TE

    Kittle is out with hamstring

    Out

  • Eddy Pineiro
    K

    Pineiro is questionable with knee

    Questionable

  • Brandon Aiyuk
    WR

    Aiyuk is out with knee

    Out

  • Jauan Jennings
    WR

    Jennings is questionable with ankle

    Questionable

  • Brock Purdy
    QB

    Purdy is out with toe

    Out

  • Jacob Cowing
    WR

    Cowing is out with hamstring

    Out

  • Jordan Watkins
    WR

    Watkins is doubtful with ankle

    Doubtful

  • Jordan James
    RB

    James is doubtful with finger

    Doubtful

Cardinals Injuries

  • Will Hernandez
    OL

    Hernandez is out with knee

    Out

  • Owen Pappoe
    LB

    Pappoe is questionable with quad

    Questionable

  • Dante Stills
    DE

    Stills is questionable with heel

    Questionable

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Player Stats
  • passing yards
    Mac Jones logo
    Mac Jones
    279
    pyds
  • passing touchdowns
    Mac Jones logo
    Mac Jones
    3
    ptd
  • rushing yards
    Christian McCaffrey logo
    Christian McCaffrey
    124
    ryds
  • rushing touchdowns
    player logo
    -
    -
    rtd
Depth Charts
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Starter2ND3RD4TH
QBBrock PurdyMac JonesKurtis Rourke
RBChristian McCaffreyIsaac GuerendoJordan James
WRJauan JenningsJacob CowingSkyy MooreJunior Bergen
TEGeorge KittleLuke FarrellJake TongesBrayden Willis
LTTrent WilliamsSpencer Burford
LGBen BartchNick Zakelj
CJake BrendelMatt HennessyDrake Nugent
RGDominick PuniConnor ColbyDrew Moss
RTColton McKivitzAusten Pleasants
LDENick BosaYetur Gross-MatosRobert Beal
RDEMykel WilliamsBryce HuffSam OkuayinonuTrevis Gipson
WLBDee WintersNick MartinJalen Graham
MLBFred WarnerLuke GiffordTatum BethuneCurtis Robinson
LCBRenardo GreenJakob Robinson
SSJi'Ayir BrownMalik MustaphaDerrick Canteen
FSJason PinnockMarques SigleSiran Neal
RCBDeommodore LenoirDarrell Luter
PThomas Morstead
PRJacob CowingJunior BergenJordan WatkinsRicky Pearsall
KRIsaac GuerendoJunior Bergen
LSJon Weeks
FBKyle Juszczyk
RWRRicky PearsallJordan WatkinsMalik Turner
NTJordan ElliottC.J. WestKalia Davis
NBUpton StoutChase Lucas
LWRBrandon AiyukRussell GageMalik Turner
DTKevin GivensAlfred CollinsSebastian ValdezEvan Anderson
Team Stats

Passing

341
YDS
532
38/54
Comps/Atts
52/74
7.093
YPA
7.514
3/1
TDs/INTs
5/2
6/42
Sacks/Yards
4/24

Rushing

228
Rush Yards
196
49
Attempts
62
4.653
YPC
3.161
1
TDs
0

Turnovers

Fumbles Lost
1
Interceptions
2

Efficiency

4/7 57.14%
Redzone
4/7 57.14%
9/22 0%
3rd Down
15/29 0%
1/1 0%
4th Down
2/2 0%

First Downs

35
Total
47
21
Pass
30
10
Rush
12
4
Penalty
5

Misc

/
Penalties/Yards
/
Possession

Cardinals vs. 49ers Odds Comparison

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Cardinals at 49ers Team Totals

MatchupOverUnder
Cardinals
2-0
N/A
N/A
49ers
2-0
N/A
N/A