Indianapolis Colts vs. San Francisco 49ers Odds & Game Pick (2021)

Oct 23, 2021 - 5:40 PM

This week’s Sunday Night Football matchup has plenty of intrigue surrounding it. Fresh off a 28-point beatdown of a lowly division rival last weekend, the Indianapolis Colts will be aiming to win their third game in four weeks. They head out to the west coast this week to take on the San Francisco 49ers. The NFL betting oddsmakers have tabbed the home side as modest favorites for this primetime showdown.

Bet risk free up to $500 on your first bet at BetStars >>


Opening Lines: 49ers -5.5; O/U 44.5
Current Lines: 49ers -4; O/U 43
Location: Levi’s Stadiums — Santa Clara, CA
Start Time: 8:20 p.m. EDT
Last Meeting: October 8, 2017 — The Colts defeated the 49ers 26-23 in Indianapolis.


If not for crazy heroics by Baltimore Ravens quarterback Lamar Jackson two weeks ago, the Colts would be entering this week’s matchup on a three-game winning streak. Instead, Indianapolis remains two games below .500 coming in. Luckily, the schedule is favorable over the next few weeks for a team that came into the year with playoff aspirations. One can’t deny that quarterback Carson Wentz seems to be settling in after being reunited with coach Frank Reich. Wentz followed up his 400-yard performance against the Ravens with another 223 through the air and two scores last week. Running back Jonathan Taylor has also looked unstoppable after a slow start to the year. He gashed the Houston Texans for 145 yards rushing last Sunday.

On the downside for the Colts offensively, the receiving corps continues to be hampered by injuries. After making his season debut and leading the team in yards last week, T.Y. Hilton was a non-participant at practice all week after suffering a new quad injury. His status for Sunday is very much in doubt. Bettors do know for a fact that Indianapolis will be without Parris Campbell. The oft-injured wideout was put back on IR with a foot injury this week after two promising games. The Colts do have a skilled pass-catching back in Nyheim Hines, but second-year receiver Michael Pittman Jr. will once again be called upon to step up especially if Hilton is ruled out.

The 49ers come into this Week 7 clash on the heels of their bye week. While many teams would probably prefer to have the bye come later in the year than Week 6, it actually came at a great time for San Francisco. After starting the year 2-0, the Niners were hit hard by injuries. Among those who missed their most recent loss two weeks ago was starting quarterback Jimmy Garoppolo. All signs point to him being back for Sunday night’s contest. This bodes well for wideouts Deebo Samuel and Brandon Aiyuk, who struggled to produce with inaccurate rookie Trey Lance under center in Week 5. 

The 49ers have also been dealing with numerous injuries on the defensive side of the ball. Unfortunately, they will remain without pass-rusher Javon Kinlaw this week. His absence will also hurt the Niners’ ability to slow down the Colts’ rushing attack. In addition, offensive tackle Trent Williams failed to practice all week and is officially doubtful to play on Sunday. 

Check out all of our NFL game previews and picks >>


  • Colts are 4-1 ATS in their last five games.
  • The total has gone over in five of the Colts’ last six road games.
  • 49ers are just 1-4 ATS in their last five games.
  • 49ers are 0-6 SU in their last six home games.
  • Colts are 6-1 ATS in their last seven games against NFC opponents.

Bottom Line

The betting ticket count has been evenly split throughout the week for this primetime matchup. At the time of writing, 53% of bets are on the Colts as a road underdog. At least some of those tickets are sharp as well, evidence in the line move. After oddsmakers opened the 49ers at -5.5, the spread has been bet down to -4. The total has also inched down slightly to a consensus line of 43 after opening at 44.5. 

While the 49ers figure to have benefitted from the bye week, the fact that they will still be without Javon Kinlaw and Trent Williams means that they will remain hindered in the trenches on both sides of the ball. Injuries were a big concern for the Colts throughout the week as well, particularly in the defensive secondary. While safety Julian Blackmon has been ruled out, both Xavier Rhodes and Andrew Sendejo practiced in full on Friday. Indianapolis has been coming into its own offensively, and that should continue this week. 

While the 49ers’ bread and butter offensively is the ground game, running the ball will be easier said than done on Sunday. The Colts enter the week ranked first in adjusted defensive efficiency against the run. Trusting Jimmy Garoppolo to make the big throws necessary to win while being without his top pass protector is difficult to do.

Pick: Colts +4 and Colts ML

Join the BettingPros Discord Chat for Live Betting Advice >>

Subscribe: Apple Podcasts | Spotify | Google Podcasts | Stitcher | RadioPublic | Breaker | Castbox | Pocket Casts

Whether you’re new to sports betting or a betting pro, our How To Bet and Sports Betting Strategy and Advice pages are for you. You can get started with our How To Section — including How to Make Money Betting on Sports — or head to more advanced strategy — like Win Totals Strategy for Sports Betting — to learn more.

Henry John is a featured writer at BettingPros. For more from Henry, check out his archive and follow him @HankTimeHenry.

The post Indianapolis Colts vs. San Francisco 49ers Odds & Game Pick (2021) appeared first on BettingPros.

No one has shouted yet.
Be the first!