Best NFL Picks and Predictions Today (How to Bet Commanders vs. 49ers on Monday Night Football in NFL Week 6)

Week 6 of the 2026 NFL season comes to a close with an interesting NFC matchup on Monday Night Football.

The San Francisco 49ers and Brock Purdy are looking to keep their undefeated season going when they host the Washington Commanders and former No. 2 overall pick Jayden Daniels.

San Francisco upset the Seattle Seahawks in Week 5, and it has one of the best offenses in the league during this perfect 5-0 start. Purdy is gaining some MVP buzz, and the 49ers have battled through several major injuries to sit atop the NFC standings.

Meanwhile, Washington tied the New York Giants in Week 5 after a late-game blunder led to the clock expiring on the team – in field goal range – in overtime. Daniels and the Commanders are now just 1-3-1 this season (0-2-1 when Daniels plays), and they need as many wins as they can get to remain in the mix to win the NFC East.

The 49ers are considerable favorites in this game, and the total is one of the highest of the week at 50.5.

In the leadup to this game, the SI Betting team has made game picks, player props selections and much more to help bettors get the most out of this matchup. I’ve decided to compile some of our favorite plays all into one spot ahead of Monday’s action.

Here’s a breakdown of each of these bets – and their latest odds in the Commanders vs. 49ers matchup.

Best NFL Picks and Predictions for Commanders vs. 49ers

Odds via DraftKings Sportsbook

San Francisco 49ers -7.5 (-110) vs. Washington Commanders – Iain MacMillan
Brock Purdy OVER 2.5 Passing Touchdowns (+146) – Peter Dewey
Jayden Daniels OVER 36.5 Rushing Yards (-109) – Peter Dewey
Mike Evans Anytime TD (-140) – Peter Dewey

San Francisco 49ers -7.5 (-110) vs. Washington Commanders – Iain MacMillan

All season long, SI Betting’s Iain MacMillan shares his favorite bet for every game in his Road to 272 column. In Week 6, he’s taking the 49ers to cover at home:

The only argument you can make to bet on the Commanders in this game, and it's not necessarily one that I'd disagree with, is that so many things have gone right for the 49ers through the first five weeks that they're bound to have a game where things go wrong. If that happens, and if Jayden Daniels can drag the Commanders' offense down the field enough, maybe Washington can cover this spread.

With that being said, that's not enough for me to take the Commanders here, and considering I expect the line to shift even more towards San Francisco this week, I'll take them at -7.5 while I still can.

There's a strong argument to be made that the 49ers are the best team in the NFL. They're second in net yards per play (+1.7), second in EPA per play, first in success rate, fourth in opponent EPA per play, and eighth in opponent success rate.

They're well-balanced on both sides of the ball, and now they get to host a bad Commanders team in a prime time slot. There's a chance this game gets ugly.

Brock Purdy OVER 2.5 Passing Touchdowns (+146) – Peter Dewey

Brock Purdy has thrown at least two scores in every game this season, and he has two games with three or more touchdown passes (against the Los Angeles Rams and Arizona Cardinals).

Washington has given up the most touchdown passes in the league (14) through five weeks, and Jameis Winston torched this secondary in the second half of Week 5.

Overall, the Commanders are 23rd in EPA/Pass and 29th in passing yards allowed in 2026.

This is a dream matchup for Purdy, who has thrown the ball just over 28 times per game for the offense that is No. 1 in success rate and No. 2 in EPA/Play this season.

At +146, I think this prop is worth a shot against one of the worst pass defenses in the NFL.

Jayden Daniels OVER 36.5 Rushing Yards (-109) – Peter Dewey

Jayden Daniels has only played in three games this season, but the Commanders quarterback has 203 rushing yards and two scores. Now, 103 of those yards came in Week 5 against the New York Giants, but Daniels has cleared this rushing yards total twice, picking up over 60 yards in two of his games.

The 49ers’ defense is a top-five unit in EPA/Rush, so I expect plenty of dropbacks for Daniels on Monday night.

Since the star quarterback has such a unique rushing ability, I wouldn’t be shocked if he escapes the pocket a few times for long scrambles.

After all, Daniels has at least five carries in every game this season, including nine in his return from a dislocated elbow.

Mike Evans Anytime TD (-140) – Peter Dewey

If I’m betting on Purdy to throw three scores, I might as well take Mike Evans to catch one!

Evans has three touchdown catches in the 2026 season, reeling in a season-high seven passes for 113 yards and a score in Week 5.

Evans remains one of the best red zone threats in the NFL because of his size, turning six targets into five receptions and two scores inside the opponent’s 20-yard-line.

Purdy has thrown multiple touchdowns in every game this season (13 overall), and the Washington defense is tied for the most passing scores allowed (14) in 2026. The Commanders are also just 23rd in the NFL in EPA/Pass.

This isn’t the best price, but Evans should have a few chances to find the end zone in Week 6.

Odds refresh periodically and are subject to change.

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