Kyle Terada-USA TODAY Sports

Kyle Terada-USA TODAY Sports

San Francisco 49ers at Arizona Cardinals odds and pick - Week 5, 2021

Oct 5, 2021 at 5:07 PM--

The San Francisco 49ers' stock went from potential contenders to hoping for a playoff spot during their two-game, home losing streak and will now go on the road to challenge the lone undefeated team in the NFL, the Arizona Cardinals, whose stock could not be higher. Here we discuss the odds and analysis from a betting perspective.

  • When: Sunday October 10th, 2021 1:25pm PT (FOX)
  • Where: State Farm Stadium, Glendale, Arizona
  • Line: 49ers +5.5, over/under 50.5

Arizona Cardinals

The Arizona Cardinals are coming off of their biggest win of the season after going into the Los Angeles Rams' home as 4-point underdogs and completely smashing LA by the score of 37-20 to emerge on top of the NFC West and the only undefeated team in the NFL.

After four weeks, Arizona ranks 10th in total DVOA (defense-adjusted value over average) adjusted for variation early (DAVE) at 9.3 percent, 8th in offensive DAVE at 6.5 percent with a 4th ranked offensive pass DVOA at 47.4 percent and 9th ranked offensive rush DVOA at -3.4 percent. The Cardinals defense is rated 14th in defensive DAVE at -1.8 percent with a 3rd rated defensive pass DVOA at -11.3 percent and 16th rated defensive rush DVOA at -11.4 percent.

Kyler Murray is 5th in defense-adjusted yards above replacement (DYAR) at 345 and 3rd in total QBR at 74.5 with 9 touchdown passes, 4 interceptions and a 76.1 completion percentage. Arizona's offensive line is 16th in run blocking with 4.19 adjusted line yards and 12th in pass protection with adjusted sack rate of 5.8 percent. The Cardinals' defensive line is 25th against the run with 4.68 adjusted line yards and 10th with an adjusted sack rate of 7.4 percent.

The Cardinals have an ESPN Football Power Index (FPI) of 3.9 and are 3-1 ATS and 2-2 to the over/under.

Kelvin Beachum, Justin Murray and Eno Benjamin are all questionable for Week 5.

San Francisco 49ers

Between injuries, penalties, the quarterback situation, offensive impotency and the 49ers' 21-28 loss to Seattle, San Francisco and its fans appear to be unraveling in Kyle Shanahan's fifth year. Trey Lance's uneven performance in the second half of the losing effort elicited a variety of strong, mixed emotions about Lance's potential and even the decision to pick him.

After four weeks, San Francisco ranks 12th in total DAVE at 7.7 percent, 11th in offensive DAVE at 4.0 percent with a 9th ranked offensive pass DVOA at 28.4 percent and 15th ranked offensive rush DVOA at -9.0 percent. The 49er defense is rated 8th in defensive DAVE at -4.9 percent with a 18th rated defensive pass DVOA at 8.1 percent and 13th rated defensive rush DVOA at -14.3 percent.

Jimmy Garoppolo is 15th in defense-adjusted yards above replacement (DYAR) at 139 and 21st in total QBR at 49.5 with 5 touchdown passes, 2 interceptions, 1 fumble lost and a 67.2 completion percentage. In the second half of Week 4, Trey Lance ran for 41 yards on 7 carries and threw for 157 yards with 2 touchdown passes and zero interceptions, completing 9 of 18 passes. San Francisco's offensive line is 13th in run blocking with 4.36 adjusted line yards and 11th in pass protection with adjusted sack rate of 5.8 percent. The Niners' defensive line is 10th against the run with 3.81 adjusted line yards and 17th with an adjusted sack rate of 6.3 percent.

The 49ers have an ESPN FPI of 2.2 and are 1-3 ATS and 2-2 to the over/under.

K'Waun Williams and Robbie Gould are out, Trent Williams, George Kittle, Josh Norman, Jimmy Garoppolo and Elijah Mitchell are questionable for Week 5.


Experienced NFL handicappers will often advise fading the public, selling high and fading overvalued teams that seem like world beaters based on recent performances and buying low on undervalued teams that make a bettor want to hold their nose if daring to pick. This approach may not always cash, but it certainly worked last week with the Jacksonville Jaguars as 7.5-point underdogs almost winning the game and losing by 3, the New York Jets as 6-point dogs winning straight up, the New York Giants as 7-point underdogs winning straight up and the New England Patriots as 7-point underdogs almost winning the game and losing by 2.

Fading a team off of a huge win was part of the strategy in bettors fading the Los Angeles Rams after a huge win against Tom Brady and the Super Bowl champion Tampa Bay Buccaneers, and the Arizona Cardinals won straight up as 4-point underdogs after opening as 6-point underdogs in Week 4, and we are not sure there could be a more pronounced sell high spot on the Arizona Cardinals than after they crushed the division favorite Rams and emerged as the only undefeated team in the league. While things could always get worse, we are also not sure San Francisco's offense could look more ineffective than it has appeared as the past two weeks.

The 49ers say Garoppolo and Trent Williams have a chance to play on Sunday with Shanahan indicating he feels more positive about Williams, but even when C.J. Beathard started the last time the Niners played in the desert against Kyler Murray, San Francisco won 20-12 as 6-point underdogs in Week 16 of 2020 and have covered three straight when underdogs at Arizona.

Whether it is Trey Sermon, who had a better game in Week 4 than he did in Week 3 with 89 yards on 19 carries against Seattle, or Elijah Mitchell, we expect Shanahan to focus on, and possibly find more success in, the run game to try and exploit Arizona's run defense and to keep the ball out of Murray's hands. While the public might expect a shootout in the desert between these teams, the final scores in the desert during the Shanahan era have been 20-12, 28-25, 18-15, 18-15, going 1-3 to the over/under, and we would lean under 50.5 if considering a total.

Prior to the start of the season, the look ahead line for this game was a pick. The current line of 5.5 is almost a touchdown swing after four games and it suggests inflated value on the Cardinals, who may be due for a bit of a let down after their gigantic win last week. The only game Arizona has not covered this season was when they were 4-point favorites at home to the Minnesota Vikings in a 1-point win, and the Cardinals would have lost if the Vikings kicker could have made a 37 yard field goal as time expired.

Win or lose, the optimal approach to sports betting is to make bets with value and with Arizona's stock at its highest and San Francisco's stock nearing a nadir, we see all the value in taking the points with San Francisco. We locked it in when we saw a +6 available and it currently sits at 5.5. The public will be all over Arizona in this spot, which could lead to the spread getting wider but that movement might get opposed by sharp action.

Pick: 49ers +5.5

2021 Season ATS: 2-2


  • What is your best bet for 49ers at Cardinals on 10/10/21?
  • 49ers +5.5
  • Cardinals -5.5
  • Over 50.5
  • Under 50.5
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