Washington Commanders vs. San Francisco 49ers Odds, Spread, Preview: NFL Week 16 Predictions

By Lawrence Smelser

Washington Commanders vs. San Francisco 49ers Week 16 matchup preview and current betting lines

The 49ers will head to Washington D.C.  to take on the Commanders on Saturday. Kickoff is slated for 4:05 p.m. ET and the matchup can be seen on CBS.

San Francisco has locked up a playoff spot at 10-7 and is currently sitting in the No. 3 seed in the NFC playoff picture. Washington (7-6-1) won’t win the NFC East with Philadelphia (13-1) and Dallas (10-4) leading the division in the top two spots.

Kyle Shanahan will attempt to beat his dad’s former team and the place where he previously served as the offensive coordinator from 2010-2013 in order to continue battling for the number two or one seed.

The 49ers are currently on a seven-game winning streak and are arguably the hottest team in the NFL. Despite quarterback Jimmy Garoppolo being done for the season due to injury, third-string QB Brock Purdy has kept the 49ers in a prime position to make a Super Bowl run.

Shanahan’s men are coming off a 21-13 win over division rivals Seattle after asserting dominance for the first three quarters. The Commanders are coming off a 19-13 loss on Sunday Night Football to the Giants.

Oddsmakers at Caesars Sportsbook give the 49ers a seven-point edge over the Commanders. On the moneyline, Washington is +260 and San Francisco is -335. Bettors have put 65% of their bets on the 49ers to cover and 95% of their money on the them to win outright. The over/under is set at 38 points.

Players to watch in the Commanders vs. 49ers contest


Terry McLaurin: The Pro Bowl wide receiver reached 1,015 yards (ninth in the NFL) last week in the loss to New York. The Commanders’ top weapon out wide now has three straight seasons with over 1,000 receiving yards. 

San Francisco

Brandon Aiyuk: The former first-round pick is now the defacto WR1 for the 49ers since Deebo Samuel is out for the remainder of the regular season. Aiyuk leads the team in receiving with 774 yards and has caught seven touchdowns so far this year.

Commanders vs 49ers prediction and odds

Our NFL bet of the week for the Commanders vs. 49ers

ESTNN is providing bettors with two free selections for this game.

Washington vs. San Francisco Alternate Spread: 49ers -7 @ -110 (Caesars)

Taylor Heinicke has had a fairy-tale run as the Commanders’ quarterback. The Old Dominion product is 5-2-1 as the starter this season but will face “Goliath” this weekend.

The 49ers boast the top-ranked defense in the NFL. The unit is both first in total defense allowing just 286.1 yards per contest and 15 points per game (9th). 

Despite losing stars such as Deebo Samuel and Garoppolo, San Francisco ranks tied for 10th on offense in terms of points per game (24.1) and is seventh in total offense (362.9 YPG).

During the team’s seven-game win streak it’s ousted quality opposition such as the Chargers, Dolphins, Buccaneers and Seahawks. Five out of the team’s seven wins have come by at least 13 or more points. 

Although Purdy was drafted as the last pick in the 2022 NFL Draft and is nicknamed “Mr. Irrelevant” the rookie has been more than relevant. As the starter, Purdy has thrown for 678 yards, six touchdowns, two interceptions and boasts a QBR of 67.9 (5th in the league). 

His head coach has worked with young talent in the past such as Heisman Trophy winners Johnny Manziel and Robert Griffin III and had high praise for him after the win over Seattle. 

The Commanders have trouble finding the end zone and are ranked 21st and 24th in total offense and in points per game and will likely have trouble against the Niners’ stout defense.

The Bay area team is 9-5 against the spread this campaign and is 5-0 ATS in its last five outings. Washington is 7-6-1 ATS in 2022.

At ESTNN, we believe San Francisco’s defense will ruffle the Commanders’ feathers and lead them to a comfortable victory. Caesars is offering -110 odds for Purdy and his offense to cover the seven-point spread.

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Commanders vs. 49ers odds: Christian McCaffrey anytime TD scorer @ -125 (Bet365)

The Pro Bowl running back has scored at least one touchdown in each of his last three games. McCaffrey is lethal both on the ground and through the air.

McCaffrey’s last three games

Week 15 at Seattle (One rushing TD)

Week 14 vs. Tampa Bay (One rushing and one receiving TD)

Week 13 vs. Miami (One receiving TD)

Since becoming the starting running back for the 49ers in week eight, the Stanford product has 22 total red zone touches (18 rushes and 4 receptions). The game script will likely favor the Niners once again so he’ll have plenty of chances against the Commanders.

Our pick is to wager McCaffrey to score a touchdown at -125 odds on Bet365 Sportsbook. If you’re interested in learning about more prop bets for week 16, read our NFL player props page.

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Frequently asked questions regarding Washington vs. San Francisco in Week 16

San Francisco selected Samuel in the second round (36th overall) of the 2019 NFL Draft. The South Carolina product has excelled in his first four years as a pro.

If you’re interested in seeing other game lines, read our NFL odds for this week page for more information. 

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