49ers vs Eagles Week 2 Picks and Predictions: Is Philly Ready to Take Flight?

Week 2 is the week of NFL betting overreactions and we may see that in Philly after a dominant Eagles win to open the season. Find out if we like a letdown in the City of Brotherly Love against the 49ers with our picks.

Last Updated: Sep 16, 2021 5:07 PM ET Read Time: 3 min
Nick Bosa San Francisco 49ers NFL
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Ahh, Week 2 of NFL betting, when opening week results can lead to overreactions from the public. We might be seeing one such line this Sunday as the Philadelphia Eagles host the San Francisco 49ers as 3-point underdogs.

The Eagles entered the season with the Over/Under on their win total set at just 6.5 but after a dominant performance in Week 1, they are seeing a short line as they welcome the Super Bowl contender 49ers to Lincoln Financial Field.

Here are our best free 49ers vs. Eagles picks and predictions for Sunday, September 19, with kickoff at 1 p.m. ET.

49ers vs Eagles odds

Odds via the Covers Line, an average comprised of odds from multiple sportsbooks.

The spread for this one has remained consistent throughout the week at 49ers -3 despite continued action on the underdog Eagles. The total has continued to grow throughout the week, from 48 on Sunday night to 50.5 as of Thursday afternoon, with action now coming in on the Under.

Use the live odds widget above to track any future line movements right up until kickoff and be sure to check out the full NFL odds before placing your bets.

49ers vs Eagles picks

Picks made on 9/16/2021 at 4:30 p.m. ET.
Click on each pick to jump to the full analysis.

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49ers vs Eagles game info

Location: Lincoln Financial Field, Philadelphia, PA
Date: Sunday, September 19, 2021
Time: 1:00 p.m. ET

49ers at Eagles betting preview


Be sure to monitor the gametime conditions with our NFL weather info.

Key injuries

49ers: Emmanuel Mosely CB (Out), Ambry Thomas CB (Out), Dre Greenlaw LB (Out), Raheem Mostert RB (Out), Jason Verrett (Out), Jeff Wilson RB (Out).
Eagles: Rodney McLeod S (Out).

Find our latest NFL injury reports.

Betting trend to know

The Under is 22-8 in the Eagles' last 30 home games. Find more NFL betting trends for 49ers vs. Eagles.

49ers vs Eagles predictions

The Eagles were 3.5-point road dogs against the Falcons last week and proceeded to demolish Atlanta by a final score of 32-6. Second-year quarterback Jalen Hurts was a force through the air (completing 27 of 35 for 264 yards and three scores) and on the ground (62 yards on seven carries). Philadelphia's pass defense also looked very effective, limiting Matt Ryan to 164 passing yards and sacking him three times. 

The 49ers came into Week 1 as sizable 8.5-point road favorites against Detroit. After jumping out to a massive 38-10 lead in the third quarter, the Niners took their foot off the pedal and a pair of Lions touchdowns in the final two minutes of the game resulted in a backdoor cover for the home side. 

Nonetheless, the 49ers looked terrific on both sides of the ball and considering that they are currently tied for fourth on the Super Bowl odds board, they might be a bit undervalued for this showdown.

Hurts may have been able to shred the Falcons secondary but he won't have an easy time against a ferocious 49ers pass rush and a pass defense that ranked fourth in the league last season despite dealing with multiple injuries.

Although Philadelphia did a good job of limiting Ryan a week ago, they looked vulnerable in the running game where they allowed 124 yards on 26 carries. Now, they'll have to deal with a typical Kyle Shanahan-coached team that does a terrific job of piling up yards on the ground, regardless of who gets the carries. Expect some regression from the Eagles and take San Fran to win and cover. 

The Over/Under for this game opened at 48 before ticking up to 50. Considering that both of these squads totaled more than 430 yards of offense in Week 1 that shouldn't be a surprise. That said, there's plenty of reason to consider going against the line movement. 

Let's not forget that both Philly and San Fran benefited from playing against two of the league's worst defenses in Atlanta and Detroit. San Francisco's stop unit is far better than the Falcons' and they will be able to bring the heat off the edge thanks to pass rushers like Nick Bosa. Although they are dealing with a few injuries on D this week, they proved last year that they have the depth to be tough even with multiple starters on the sidelines. 

As for the Eagles, while they have lots of question marks at linebacker they have a very strong defensive line led by Fletcher Cox and Javon Hargrave, who do an excellent job of getting a push up the middle. The Eagles' defense might not be great, especially when it comes to stopping the run, but it's still superior to the Lions' toothless unit.

With the Eagles going 8-22 O/U in their last 30 games at home, take the Under on Sunday. 

When healthy, the Niners' defense is one of the best around but they suffered a big loss last week with a season-ending injury to cornerback Jason Verrett, while Emmanuel Mosey is looking doubtful as well. 

That would make the Niners thin on the outside as they deal with a speedy group of Eagles receivers. Last year's Heisman Trophy winner DeVonta Smith had an impressive debut performance last week totaling six catches for 71 yards.

He also had eight targets in the passing game despite a run-focused game script during the second half. Don't expect to see the Over/Under on his receiving yards total this low for long as he builds even more rapport with Hurts as the season goes on. 

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