The Arizona Cardinals vs San Francisco 49ers matchup brings two NFC West rivals together in one of the most interesting games on the NFL Week 3 schedule.
San Francisco enters the game undefeated at 2–0, while Arizona is 1–1 after splitting its opening two games.
The 49ers have opened the season with wins over the Los Angeles Rams and Miami Dolphins, while the Cardinals defeated the Los Angeles Chargers before suffering a difficult loss to the Seattle Seahawks.
Now Arizona travels to Levi’s Stadium for its first NFC West matchup of the 2026 season.
The game is scheduled for Sunday, September 27, 2026, at 4:05 PM ET / 1:05 PM PT. FOX will carry the game nationally in the designated regional broadcast window.
Cardinals vs 49ers Game Information
| Detail | Information |
|---|---|
| Matchup | Arizona Cardinals vs San Francisco 49ers |
| Date | Sunday, September 27, 2026 |
| Kickoff | 4:05 PM ET |
| Pacific Time | 1:05 PM PT |
| Central Time | 3:05 PM CT |
| Venue | Levi’s Stadium |
| Location | Santa Clara, California |
| TV | FOX |
| Streaming | NFL+ / FOX options depending on market |
| Cardinals Record | 1–1 |
| 49ers Record | 2–0 |
| Cardinals QB | Jacoby Brissett |
| 49ers QB | Brock Purdy |
The 49ers’ official schedule confirms the September 27 home matchup at Levi’s Stadium, with FOX carrying the game.
Cardinals vs 49ers Records
Arizona Cardinals: 1–1
Arizona opened the 2026 season with a 26–14 victory over the Los Angeles Chargers.
The Cardinals then returned home to face the Seattle Seahawks in Week 2 but struggled offensively in a 35–13 loss.
Arizona enters Week 3 averaging:
- 16.5 points per game
- 272 total yards per game
- 67.7% quarterback completion rate
- 372 passing yards from Jacoby Brissett
- +2 turnover differential
The biggest concern is the offense’s production after the Week 2 loss.
Arizona managed only 151 total yards against Seattle, making offensive efficiency a major storyline entering San Francisco.
San Francisco 49ers: 2–0
San Francisco has looked extremely efficient to begin the season.
The 49ers defeated the Rams 27–7 in Week 1 and followed that with a 35–13 victory over Miami in their home opener.
Through two games, San Francisco is averaging:
- 31.0 points per game
- 380.5 yards per game
- 492 passing yards from Brock Purdy
- 5 passing touchdowns
- 1 interception
- +1 turnover differential
The 49ers have also been extremely efficient in the red zone and have yet to allow a sack through two games, according to current Week 3 analysis.
Brock Purdy vs Jacoby Brissett
The quarterback matchup is one of the biggest statistical differences between these teams.
Brock Purdy
Purdy has been outstanding during San Francisco’s 2–0 start.
Through two games, he has:
- 492 passing yards
- 5 touchdowns
- 1 interception
- 80.4% completion rate
Against Miami in Week 2, Purdy completed 20 of 22 passes for 287 yards and two touchdowns, producing a 149.1 passer rating.
His Week 2 performance earned him NFC Offensive Player of the Week honors.
Purdy’s accuracy and ability to distribute the football efficiently have been central to San Francisco’s strong start.
Jacoby Brissett
Brissett has completed 67.7% of his passes through two games and has thrown for 372 yards, two touchdowns and one interception.
The Cardinals will need considerably more production from their passing game against San Francisco.
Brissett completed only 17 of 28 passes for 95 yards in the Week 2 loss to Seattle.
Christian McCaffrey vs Cardinals Defense
Christian McCaffrey remains one of the biggest names in this matchup.
Through two games, he has recorded:
- 91 rushing yards
- 20 carries
- 2 rushing touchdowns
- 4.6 yards per carry
McCaffrey also remains an important receiving option in San Francisco’s offense.
The Cardinals will have to account for him both between the tackles and in the passing game.
San Francisco’s ability to use McCaffrey as both a runner and receiver can force Arizona’s defense to make difficult coverage decisions.
The 49ers’ official Week 3 preview also highlights McCaffrey’s role as part of the team’s focus on offensive consistency.
Trey McBride Could Be Arizona’s Biggest Weapon
The Cardinals have one of the league’s most productive tight ends in Trey McBride.
Through two games, McBride has:
- 17 receptions
- 136 receiving yards
- 2 touchdowns
His 17 receptions make him one of the most heavily utilized targets in Arizona’s offense.
McBride could be particularly important against San Francisco because Arizona may need to rely on short and intermediate passing plays to maintain possession.
If the Cardinals can consistently get McBride involved, they could potentially slow the game down and keep their offense on the field.
49ers Receiving Corps
San Francisco has multiple receiving options around Purdy.
Mike Evans currently leads the 49ers with 103 receiving yards and one touchdown through two games.
However, Evans is dealing with a hip injury and did not participate in Wednesday’s practice.
Demarcus Robinson also did not practice Wednesday because of an ankle issue.
That makes the injury situation at wide receiver something to watch closely before kickoff.
San Francisco also has other receiving options capable of absorbing additional targets if necessary.
Cardinals vs 49ers Key Stats
| Category | Cardinals | 49ers |
|---|---|---|
| Record | 1–1 | 2–0 |
| Points/Game | 16.5 | 31.0 |
| Yards/Game | 272.0 | 380.5 |
| Passing Leader | Jacoby Brissett | Brock Purdy |
| Passing Yards | 372 | 492 |
| Passing TDs | 2 | 5 |
| INTs | 1 | 1 |
| Leading Rusher | Tyler Allgeier | Christian McCaffrey |
| Leading Receiver | Trey McBride | Mike Evans |
| Turnover Differential | +2 | +1 |
The early statistical gap is significant: San Francisco is averaging 31 points and 380.5 yards per game, compared with Arizona’s 16.5 points and 272 yards.
49ers Defense vs Cardinals Offense
San Francisco’s defense has also played well during the opening two games.
The 49ers allowed only seven points to the Rams in Week 1 and 13 points to Miami in Week 2.
The defense has recorded four sacks and one interception through two games.
Arizona’s offense will have to find a way to avoid long third downs and negative plays.
The 49ers have also not allowed a sack this season, meaning their offensive line has been particularly effective at keeping Purdy protected.
Cardinals Defense vs 49ers Offense
Arizona’s defense faces one of its toughest tests of the young season.
The Cardinals will have to deal with:
- Brock Purdy
- Christian McCaffrey
- Mike Evans
- Trey McBride’s former 49ers connection? No — McBride is Arizona’s weapon
- A San Francisco offensive system built around spacing and yards after the catch
The biggest objective will be preventing San Francisco from controlling the game through efficient drives.
If the 49ers consistently stay ahead of the chains, Arizona could spend a significant portion of the afternoon defending.
Cardinals vs 49ers Injury Report
Injuries are an important part of the Week 3 matchup.
Arizona Cardinals
Arizona’s Wednesday report included:
- Roy Lopez — groin — DNP
- Max Melton — toe — DNP
- Isaac Seumalo — rest — DNP
- Josh Sweat — rest — DNP
- Dadrion Taylor-Demerson — back — DNP
- Hjalte Froholdt — knee — limited
- Garrett Williams — Achilles — limited
- Mack Wilson Sr. — rest/thumb — limited
- Jacoby Brissett — hip — full
The Cardinals also announced that cornerback Will Johnson was lost for the season, while Max Melton’s status was uncertain after a toe injury.
San Francisco 49ers
San Francisco’s Wednesday report included:
- Nick Bosa — rest/knee — DNP
- Mike Evans — hip — DNP
- Dre Greenlaw — rest/Achilles — DNP
- Romello Height — hand — DNP
- Christian McCaffrey — rest — DNP
- Demarcus Robinson — ankle — DNP
- James Thompson Jr. — ankle — DNP
- Trent Williams — rest — DNP
These were practice statuses rather than final game designations. The official Friday report and inactive list should be checked before kickoff.
Cardinals vs 49ers Betting Odds
Current published sportsbook information has San Francisco as a substantial home favorite.
A recent market snapshot lists:
- 49ers -8.5
- Cardinals +8.5
- 49ers moneyline around -470
- Cardinals moneyline around +360
- Over/Under 47.5
FanDuel’s current Week 3 preview also lists San Francisco at -8.5 with a 47.5-point total and gives its model an 80.68% win probability. That percentage is a model output, not a guarantee of the game result.
Betting lines can change before kickoff.
Cardinals vs 49ers Prediction
This matchup has a clear statistical contrast.
Arizona is 1–1, but the Cardinals struggled badly offensively in Week 2.
San Francisco, meanwhile, is averaging 31 points per game and has already produced two convincing wins.
Brock Purdy’s efficiency is another major factor.
The 49ers quarterback is completing more than 80% of his passes, while San Francisco has not allowed a sack through two games.
Arizona’s best route to keeping this game competitive may be to control possession, get Trey McBride involved and avoid giving San Francisco short fields.
The Cardinals also have a positive turnover differential, which could help them stay within the number.
However, San Francisco has more offensive firepower and is playing at home.
Projected Score
San Francisco 49ers 30, Arizona Cardinals 17
Cardinals vs 49ers Prediction Breakdown
| Category | Statistical Edge |
|---|---|
| Quarterback | 49ers |
| Passing Offense | 49ers |
| Receiving Depth | 49ers |
| Running Game | 49ers |
| Total Offense | 49ers |
| Recent Momentum | 49ers |
| Defense | 49ers |
| Turnover Differential | Cardinals |
| Home Field | 49ers |
| Overall Early-Season Production | 49ers |
The Cardinals’ +2 turnover differential is one area where Arizona has the early statistical advantage.
Players to Watch
Brock Purdy
Purdy enters Week 3 with 492 passing yards and five touchdowns while completing 80.4% of his passes.
Christian McCaffrey
McCaffrey has two rushing touchdowns and remains central to San Francisco’s offensive game plan.
Trey McBride
McBride leads Arizona with 136 receiving yards and two touchdowns.
Jacoby Brissett
Brissett needs a bounce-back performance after throwing for only 95 yards in Week 2.
Mike Evans
Evans leads San Francisco in receiving yards but enters the week dealing with a hip injury.
Nick Bosa
Bosa’s health and availability could be important against Arizona’s offensive line.
Key Matchups
1. Brock Purdy vs Cardinals Secondary
Purdy’s accuracy has been exceptional through two games. Arizona needs to disrupt his rhythm without giving up explosive plays.
2. Trey McBride vs 49ers Linebackers
McBride has already become a major part of Arizona’s passing attack.
3. Christian McCaffrey vs Cardinals Front
Arizona must limit McCaffrey’s efficiency on early downs.
4. 49ers Offensive Line vs Cardinals Pass Rush
San Francisco has not allowed a sack through two games. Arizona needs to change that.
5. Arizona Offensive Line vs 49ers Defensive Front
Brissett could face significant pressure if Arizona falls behind and becomes one-dimensional.
How to Watch Cardinals vs 49ers
The game will be played on Sunday, September 27, 2026.
Kickoff
4:05 PM ET / 3:05 PM CT / 1:05 PM PT
TV
FOX
Stadium
Levi’s Stadium
Location
Santa Clara, California
The 49ers’ official broadcast information confirms the FOX broadcast and 1:05 PM PT kickoff. NFL+ is also listed as an available option for eligible live local and regular-season games on mobile devices.
Cardinals vs 49ers Head-to-Head
The Cardinals and 49ers are NFC West rivals and meet regularly as division opponents.
That divisional familiarity means Arizona will have a better understanding of San Francisco’s tendencies than a typical nonconference opponent.
However, the current matchup comes with San Francisco entering 2–0 and Arizona at 1–1.
The 49ers are also playing their second consecutive home game after defeating Miami 35–13 in their Week 2 home opener.
Cardinals vs 49ers Fantasy Football
Brock Purdy
Purdy’s accuracy and touchdown production give him significant fantasy upside.
Christian McCaffrey
McCaffrey remains one of the most important fantasy players in the matchup because of his rushing and receiving involvement.
Trey McBride
McBride has 17 receptions through two games and is one of Arizona’s safest volume-based fantasy options.
Mike Evans
Evans has 103 receiving yards and one touchdown, but his injury status needs to be monitored.
Jacoby Brissett
Brissett is a more difficult fantasy option because Arizona’s passing offense struggled in Week 2.
What Could Decide Cardinals vs 49ers?
1. Can Arizona protect Brissett?
San Francisco’s defensive front can create problems if Arizona falls behind.
2. Can the Cardinals slow McCaffrey?
San Francisco’s offense becomes more difficult to defend when McCaffrey is producing both as a runner and receiver.
3. Can Trey McBride maintain his volume?
Arizona needs sustained drives, and McBride can be a major part of that plan.
4. Turnovers
Arizona enters with a +2 turnover differential. Extra possessions could be critical against San Francisco.
5. Third-Down Efficiency
San Francisco’s ability to sustain drives could determine whether Arizona gets enough offensive possessions to keep the game close.
Cardinals vs 49ers FAQs
When is Cardinals vs 49ers?
The game is scheduled for Sunday, September 27, 2026.
What time is Cardinals vs 49ers?
Kickoff is 4:05 PM ET, 3:05 PM CT and 1:05 PM PT.
Where is Cardinals vs 49ers being played?
The game will be played at Levi’s Stadium in Santa Clara, California.
What channel is Cardinals vs 49ers on?
The game will be broadcast on FOX.
What are the Cardinals’ and 49ers’ records?
Arizona is 1–1, while San Francisco is 2–0 entering Week 3.
Who is the Cardinals quarterback?
Jacoby Brissett is Arizona’s quarterback.
Who is the 49ers quarterback?
Brock Purdy is San Francisco’s quarterback.
Who leads the Cardinals in receiving?
Trey McBride leads Arizona with 136 receiving yards through two games.
Who leads the 49ers in passing?
Brock Purdy has thrown for 492 yards and five touchdowns through two games.
Who is favored in Cardinals vs 49ers?
Current published betting markets have the 49ers favored by approximately 8.5 points.
What is the Cardinals vs 49ers over/under?
The current published total is approximately 47.5 points.
What is the Cardinals vs 49ers prediction?
The projected score for this preview is:
49ers 30, Cardinals 17.
Final Cardinals vs 49ers Prediction
The Cardinals have enough talent to make this NFC West matchup competitive, particularly if they can force turnovers and get Trey McBride heavily involved.
But San Francisco enters Week 3 with a substantial statistical advantage.
The 49ers are undefeated, averaging 31 points per game, while Brock Purdy is completing more than 80% of his passes.
Arizona’s offense, meanwhile, produced only 151 total yards in Week 2.
The Cardinals will need a significantly better offensive performance to keep pace with a San Francisco team that has already scored 62 points through its first two games.
Playing at Levi’s Stadium adds another factor.
Final Prediction
San Francisco 49ers 30 – Arizona Cardinals 17
Cardinals vs 49ers — Sunday, September 27, 2026 — 4:05 PM ET / 1:05 PM PT — FOX