49ers Cardinals Bet Tips for Week 16

Last Updated: Jan 8, 2021

The San Francisco 49ers visit the Arizona Cardinals at State Farm Stadium on Saturday at 4:30 p.m. ET. Here’s our complete guide to 49ers Cardinals Bet Tips. Odds and lines for 49ers-Cardinals picks are from PointsBet, current as of Monday at 4:30 p.m. ET.

San Francisco 49ers (5-9) at Arizona Cardinals (8-6)

49ers Cardinals Bet Tips

Odds & Betting Lines for 49ers-Cardinals Picks

  • Against The Spread: Cardinals -3.5 (-110)/49ers +3.5 (-110)
  • Moneyline: Cardinals (-191)/49ers (+160)
  • Total: 49 — Over 49 (-115)/Under 49 (-109)
  • Implied Team Totals: Cardinals 26.75, 49ers 22.25

The 49ers are 1-6 in their past seven games, losers of three straight. They will look to pick up a win and play spoiler on their NFC West foes, the Cardinals, a team that holds the seventh and final playoff spot in the NFC.

This is a must-win matchup for the Cardinals as they are one game up on the Bears, a team that has won two consecutive games and can knock the Cardinals out of the No. 7 seed if Chicago continues their recent winning ways and Arizona drops one. The Cardinals have been victorious in two straight, following a three-game losing streak.

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49ers-Cardinals Key Injuries


Last week, the 49ers designated TE George Kittle to return from the injured reserve list. He’s been sidelined since Week 8 with a foot injury. However, while he had returned to practice last week, he did not play against the Cowboys. With the 49ers’ playoff chances dead and buried, there is a good chance Kittle does not see the field again this season. However, anything is possible.

While Kittle is unlikely to play Saturday, Raheem Mostert and Jeff Wilson are both on the injury report with ankle injuries. While Wilson’s is not considered serious, Mostert is legitimately questionable to play against the Cardinals.

If Mostert sits, Wilson and Tevin Coleman will handle the primary running back duties in Week 16.


The Cardinals are not dealing with any new significant injuries that would impact 49ers-Cardinals Picks.

49ers-Cardinals Players to Watch

49ers WR Brandon Aiyuk is flying under the radar as one of the best rookie wideouts of 2020. While Justin Jefferson is getting all the accolades, Aiyuk is quietly producing in a big way.

In nine of his 11 games played, Aiyuk has scored a touchdown or has gone for 100+ receiving yards, accomplishing that feat in 9-of-10 games since Week 3. What’s even more remarkable is the fact that Aiyuk has been performing no matter who is under center for the 49ers or what members of their supporting cast are healthy.

Aiyuk has been the team’s primary receiver for most of the year and has come through. Look for Aiyuk to continue his streak of seven straight games with a score or 100+ yards against a Cardinals defense allowing the 12th fewest passing yards per game.

49ers Cardinals Bet Tips and 49ers-Cardinals Picks: 49ers WR Brandon Aiyuk, pictured here celebrating a touchdown in Week 12, will be a key part of saving San Francisco's dying playoff hopes. (49ers-Cardinals Picks and 49ers Cardinals Bet Tips)
49ers-Cardinals Picks: San Francisco 49ers wide receiver Brandon Aiyuk (11) celebrates a touchdown against the Buffalo Bills during the first half at State Farm Stadium. (Joe Camporeale, USA TODAY Sports)

While the Cardinals are not surrendering a ton of yards to wide receivers, they are giving up the fifth-most touchdowns to the position (16). Aiyuk has scored a touchdown in five of his past seven games.

The Cardinals have won each of their past two games. Consequentially, DeAndre Hopkins went ballistic in both of those wins. In both Week 14 and 15, Hopkins saw 11 targets, catching nine of them for at least 136 yards, topping out at 169 yards with a touchdown last week.

While Hopkins is coming off back-to-back games with 136+ yards, those big-yardage outings snapped a three-game streak finishing with fewer than 55 yards. Again, consequentially, the Cardinals lost all of those games.

Hopkins is an elite receiver and as long as he is heavily featured as he should be, this Cardinals offense will go. In his only career game against the 49ers as a member of the Cardinals back in the 2020 season opener, Hopkins hung a 14/151/0 line on the 49ers on 16 targets.

Hopkins also went for an 11/149/2 line on San Francisco back in a 2017 meeting with the 49ers as a member of the Texans.

49ers Cardinals Weather Report

The weather at State Farm Stadium will not impact the outcome of the game as it is a dome.


49ers-Cardinals Picks & Best Bet

BEST BET: Cardinals (-191)

While I do believe the Cardinals should dominate this football game, I am not too sure about it. I do, however, believe they will win outright. After all, the Cardinals need this game as they are hanging on the No. 7 seed in the NFC by a thread with the Bears one game back.

While the 49ers could play spoiler, I don’t think they get the job done. The 49ers are 1-6 in their past seven games straight up, losers of three straight. The 49ers have also given up 34+ points in two of their past three games, including 41 to the Cowboys last week. If Dallas can hang 41 on the 49ers, the Cardinals’ offense should pop if they let Kyler Murray loose.

While the Cardinals are 3-3 in their past six games, they are on a two-game winning streak, which snapped a three-game slide.

Murray is 1-2 as the Cardinals starter versus the 49ers, but both of his losses were last season when he was a rookie and the 49ers were the NFC champions. Things are not the same this year for either club. We saw that in Week 1 in which Murray not only picked up the win, but he also dropped 230 yards and a touchdown on the 49ers with his arm while gashing them for 91 rushing yards and another score with his legs. He also threw a pick in the victory.

The Cardinals are 8-2 straight up against the 49ers in their past 10 meetings.

CONSIDER: Over 49 (-115)

In the Week 1 meeting between the 49ers and Cardinals, the total was set at 48.5 points and it went Under by a score of 24-20. However, since that outing, the 49ers defense, and the team as a whole, has been decimated by injuries.

Meanwhile, the Cardinals have exploited Kyler Murray’s mobility to the fullest as he’s been one of, if not, the most dangerous dual-threat signal-caller when he is on.

The Cardinals have the 10th best scoring offenses in the NFL at a rate of 27.9 points per game. And while the San Francisco offense had fallen off from last season, which is expected due to all their ailing players, they can still score the football in the right matchup. The 49ers have scored 24+ points in two of their past four games, including 31 in last week’s loss to Dallas.

The Over is 4-3 in the 49ers’ past seven games, hitting last week versus the Cowboys.

The Over is 5-3 in the Cardinals’ past eight games and 2-1 in their past three, hitting last week against Philadelphia.

The Over is 3-2 in the past five meetings between the Cardinals and 49ers and 2-1 in their past three, failing to hit in their Week 1 encounter.

The Over is 5-0 in Cardinals’ past 5 home games.

CONSIDER: 49ers +3.5 (-110)

Although I think the Cardinals will win this game outright, I am n to sure how much I trust them to cover the 3.5 points. If it was three, I would be more apt to take it.

In three of the past four meetings between the Cardinals and 49ers, the margin of winning was fewer than four points with the Cardinals winning two of them.

The Cardinals are 5-0-1 against the spread in their past six meetings with the 49ers.

The 49ers are 1-6 ATS in their past seven games, failing to cover in three straight.

The Cardinals have covered the spread in two consecutive games following five straight outings failing to cover.

Anthony Cervino is 55-44-1 on his NFL Best Bets in 2020.

Prepare Week 16 betting tips and plan

After studying 49ers Cardinals Bet Tips and 49ers-Cardinals Picks:

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Anthony Cervino

Anthony Cervino is an NFL Writer and Betting Analyst for The Game Day. He is also a lifelong NFL savant and self-proclaimed league historian. In the industry, Anthony has excelled in both the fantasy football and sports betting space with fantasy his proverbial bread and butter. Anthony has made appearances on SiriusXM, amongst other publications. He is also the co-creator of the FF Faceoff (Faceoff Sports Network) and the FF Faceoff Mental Health Podathon partnered with the Hayden Hurst Foundation. Industry Clout: 15th most accurate ranker in the FantasyPros ECR for both draft and in-season accuracy (2019) | 8th most accurate ranker in the FantasyPros ECR for sleepers (2020) | 13th most accurate ranker in the FantasyPros ECR for in-season accuracy, including 2nd at quarterback and 3rd at tight end (2021).

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