Cardinals vs. 49ers Odds & Betting Predictions - September 21, 2025
Cardinals at 49ers
8:25 pm • FOXCardinals at 49ers Odds
Spread, Total, Moneyline
MatchupOpenSpreadTotalMoneyline | ||||
|---|---|---|---|---|
 Cardinals 2-2 | +3.5 | +1.5-110 | o44.5-110 | +105 |
 49ers 4-1 | u47.5 | -1.5-110 | u44.5-110 | -125 |
Levi's StadiumSanta Clara
Cardinals vs. 49ers Expert Picks
💰🦡 Jake
Last 30d: 101-128-6 (+23.6u)
Under 42 (Live)+750
22.5u
Gamblers Dream
Last 30d: 4-5-0 (+10.9u)
SF +230 (Live)
5.75u
Final drive 3 to win. Be a hero Mac.
Ryan Sura
Last 30d: 99-94-2 (+7.7u)
ARI +3-141
1.06u
Mjaybrod
Last 30d: 68-84-3 (-10.1u)
SF -120
0.83u
Mac Jones ML
The Degenerates
Last 30d: 72-62-2 (+4.9u)
SF -2.5-115
1.15u
Vegas Refund
Last 30d: 36-36-2 (-3.7u)
ARI +1.5-110
1u
Babs .
Last 30d: 79-70-1 (+8.9u)
J.Tonges o2.5 Recs+105
1u
Matthew Freedman
Last 30d: 30-37-0 (-5.9u)
Over 44.5-108
1.08u
Projection: 46.3. For more, check out the Fantasy Life game model.
Capper Central
Last 30d: 94-56-1 (+24.5u)
ARI +2.5-110
1u
Matthew Freedman
Last 30d: 30-37-0 (-5.9u)
C.McCaffrey Anytime TD Scorer Yes-177
0.89u
Projection: -233. For more, check out the Fantasy Life player projections.
Shady Biev
Last 30d: 28-37-1 (-8.7u)
ARI +2.5-115
1.5u
Scott Rickenbach
Last 30d: 55-58-2 (-11.2u)
ARI +2.5-115
0.87u
Sean Zerillo
Last 30d: 148-170-6 (-11.0u)
SF -1.5-107
0.27u
Royals Props
Last 30d: 23-22-1 (-2.6u)
M.Harrison o47.5 Rec Yds-115
1.15u
MGM
Matt Moore
Last 30d: 14-15-1 (-2.0u)
K.Murray Anytime TD Scorer Yes+380
0.25u
Via @GDAWG5000
Gilles Gallant
Last 30d: 22-69-0 (-8.6u)
K.Murray Anytime TD Scorer Yes+380
1u
Let’s Ride!
Kenny Ducey
Last 30d: 28-25-2 (+1.3u)
ARI +2.5-105
1u
Roger Goodell
Last 30d: 47-33-2 (+7.8u)
SF -120
0.83u
Chris Raybon
Last 30d: 23-25-1 (+11.0u)
SF +1.5-115
1u
▶️ 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
Last 30d: 44-58-0 (-11.6u)
SF +100
1u
FTN Fantasy
Last 30d: 74-69-1 (+2.3u)
SF +100
1u
SF +1-110
0.91u
Top Shelf Action 🥃
Last 30d: 90-109-1 (-27.3u)
Under 43.5-110
0.91u
Cardinals vs. 49ers Previews & Analysis
Cardinals vs. 49ers Props
Prop Projections
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Prop Odds Comparison
Line Movement Tracker
Cardinals vs. 49ers Public Betting Percentages
Betting Trends
- 49ers are 4-1 in their last 5 games.
- 49ers are 3-2 in their last 5 games against the spread
- 49ers are 3-0 in their road games against the spread
- The totals have gone OVER in 3 of 49ers' last 5 games
- The totals have gone OVER in 1 of 49ers' 2 last games at home
Matchup History
Against the Spread (ATS) History
Over/Under History
Last 5 Matchups
49ers vs. Cardinals Injury Updates
49ers Injuries
- George KittleTE
Kittle is out with hamstring
Out
- Brandon AiyukWR
Aiyuk is out with knee
Out
- Jauan JenningsWR
Jennings is out with ankle
Out
- Brock PurdyQB
Purdy is out with toe
Out
- Ricky PearsallWR
Pearsall is out with knee
Out
- Jacob CowingWR
Cowing is out with hamstring
Out
- Jordan WatkinsWR
Watkins is doubtful with ankle
Doubtful
- Jordan JamesRB
James is doubtful with finger
Doubtful
Cardinals Injuries
- James ConnerRB
Conner is out with foot
Out
- Greg DortchWR
Dortch is questionable with collarbone
Questionable
- Owen PappoeLB
Pappoe is questionable with quad
Questionable
- Trey BensonRB
Benson is out with knee
Out
Team Stats
Cardinals vs. 49ers Odds Comparison
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Cardinals at 49ers Team Totals
MatchupOverUnder | ||
|---|---|---|
Cardinals 2-2 | o22-113 | u22-115 |
49ers 4-1 | o23.5-103 | u23.5-125 |