49ers vs. Cardinals Point Spread: NFL Week 5 Odds, Prediction

Nik Kowalski | Updated Oct 07, 2021

Kyler Murray's MVP-calibre start to the season has helped Arizona remain the last undefeated team in the NFL heading into Week 5.

October 10, 2021, 4:25 PM ET
State Farm Stadium
Pointspread +5.5 -107
Moneyline +230
Over / Under o +48.5


Betting Action


Pointspread -5.5 -113
Moneyline -279
Over / Under u +48.5


Betting Action


As Jimmy Garoppolo deals with a calf strain it’s opened up the door for 2021 third-overall pick Trey Lance to possibly make his first career start against the league’s last undefeated team, the Arizona Cardinals. Whoever is under centre Sunday afternoon, they’ll need to keep with Arizona as the 4-0 Cardinals also lead the NFL with 35 points per game. Kyler Murray’s one of the MVP front-runners with a league-best 76.1 completion percentage and 1,273 yards in four games.

The Cardinals are 5.5.-point favourites to win on the NFL odds, with a total of 50.0.  Kickoff at State Farm Stadium begins at 4:25 p.m. EST.

NFL Point Spread and Betting Analysis

The undefeated Cardinals are also winning at a .750 clip against the spread, with their lone spread loss coming in their only home game back in Week 2. Arizona’s 5-1 against the spread in their last six October games and are 6-3-1 against the spread in their last 10 against the 49ers.

When it comes to the total, Arizona’s elite offence is being accounted for with both the over and under hitting twice in their 2021 games. San Francisco holds the same over-under record, yet rank seventh in points per game with 26.8 (remember Arizona’s first with 35).

San Francisco 49ers

Before getting injured, Garoppolo was playing sound football. The eighth-year quarterback has a 66.1 completion percentage, 925 yards, and a 5 to 2 touchdown to interception ratio through four games. When Lance came in midway through San Fran’s 28-21 home loss to Seattle, he threw for 157 yards on nine of 18 passing… but keep in mind, 76 of those yards came on a touchdown strike to Deebo Samuel in which the Seahawks blew a coverage.

If Garoppolo is healthy enough, he’ll be Kyle Shanahan’s guy for now. And if Garoppolo is out there, Samuel is his guy as he leads all receivers with 490 yards through a month of football.

Along with Garoppolo, star left tackle Trent Williams and tight end George Kittle missed practice Wednesday.

Arizona Cardinals

Week 4 was a prove-it game for the Cardinals, who at the time were 3-0 and travelling to L.A. to play the 3-0 Rams. Arizona sure proved their top-tier status too, blowing out the Rams 37-20. Murray threw for 268 yards and two scores, while Arizona rushed for 216 yards, including 120 from Chase Edmonds and two rushing scores from James Conner.

Entering Week 5, A.J. Green leads the team with 248 receiving yards but four different Cardinals receivers have over 200 yards. This itself proves the talent across the board on Arizona’s roster. On defence, guys like cornerback Byron Murphy and defensive end Chandler Jones are stepping up with two interceptions and five sacks on the year respectively.

NFL Prediction: Who Will Win 49ers vs. Cardinals?