Cardinals vs 49ers Preview: San Francisco Biggest Favorite of Week 4
Arizona is 3-0 against the spread after upset of Dallas

Despite a 1-2 start, the Arizona Cardinals have been a pleasant surprise under new head coach Jonathan Gannon. But they’ll face a serious test Sunday (4:25 p.m. ET) when they visit NFC rival San Francisco.
At -14 (-110), the 49ers are currently the biggest favorite on the NFL’s Week 4 slate. They’re also -850 on the moneyline. Arizona, meanwhile, is +14 (-110) on the spread and +625 to pull off the upset. The projected total is 44 (-111 Over, -109 Under), up from 41.
Read on as we break down this NFL matchup in our Cardinals vs 49ers preview.
Arizona Cardinals at San Francisco 49ers 
Day/Time:
Location: Levi’s Stadium; Santa Clara, Calif.
Streaming: Fox
Betting Trends
The Arizona Cardinals have covered the spread in all three games this season and are 5-1 ATS in their last six games. But they are just 1-8 ATS in their previous nine games against NFC West opponents. Meanwhile, the San Francisco 49ers are 11-3 ATS in their last 14 games, including 2-1 this NFL season. The 49ers have covered eight straight games at home. Also, the total has gone Under in four of their last five contests. That’s important to remember when assessing the NFL odds this week.
Arizona Ahead of the Game
The Arizona Cardinals pulled off the biggest upset of Week 3, defeating the Dallas Cowboys 28-16 an as 11-point underdog. Joshua Dobbs threw for 189 yards and a touchdown on 17 of 21 passing and also ran for 55 yards, as the Cardinals improved to 3-0 ATS.
The Cardinals (1-2) were widely thought to be among the NFL’s worst teams, with a projected win total of 5.5. They still could be, but they’re certainly holding their own in the early going under first-year head coach Jonathan Gannon. In Week 2, the Cardinals jumped out to a 20-0 halftime lead as a 4.5-point underdog against the New York Giants before falling 31-28 on a last-minute field goal.
James Conner has helped pace Arizona’s offense, rushing for 266 yards (5.2 yards per carry) and two touchdowns per NFL stats. He was limited Wednesday due to a back injury, which is worth monitoring as you assess the odds in our Cardinals vs 49ers preview.
The Cardinals have lost nine of their last 10 games dating to last season, including six of seven on the road. That futility led many to assume they’d be in line for the No. 1 pick in the 2024 NFL draft. But given their start under Gannon, it’s clearly too early to jump to such conclusions.
A League of Their Own
The San Francisco 49ers are 3-0 (2-1 ATS) on the season after pounding the Giants 30-12 last Thursday as a 10.5-point favorite. Now they get extended rest to face their NFC West rivals. The Cardinals have won 11 of the previous 16 meetings, but these are vastly different circumstances.
The 49ers are among the best teams in the NFL. They might even be the team to beat. In fact, they’re favored to win the NFC (+250) and are a +650 co-favorite with the Kansas City Chiefs to win Super Bowl LVIII.
Their success is no surprise. The 49ers were projected for 11.5 wins, matching the highest total in the league. They’ve scored 30 points in their first three games and rank fourth in the NFL in total offense (399 yards per game). Christian McCaffrey has been a catalyst for San Francisco, with a league-leading 353 rushing yards. The All-Pro running back is also among the NFL leaders in total yards with 423.
The 49ers are 15-1 in their last 16 games dating to last season, including 11-1 in their last 12 against NFC opponents. That sustained success carries a lot of weight. Keep that in mind when analyzing the odds in our Cardinals vs 49ers preview.
Handicapping the Preview
Gannon deserves credit for the work he’s done in Arizona. He’s helped galvanize a team that most pegged as a bottom-feeder. The Cardinals are still a longshot to do any real damage — for example, they’re +5000 to win the NFC West — but the early returns are promising.
That said, San Francisco is a legitimate Super Bowl contender, maybe even the favorite. And while the Cardinals upset another contender in Dallas, it’s best not to overreact from week to week. The Cardinals are in for a cold dose of reality when they visit San Francisco. Look for the 49ers to win by two touchdowns.
For NFL betting news, odds, analysis and more, visit Point Spreads Sports Magazine.
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