San Francisco 49ers And 3 Other Fantasy Football Must-Start Week 2 Defenses

There were many standout defenses in fantasy football in Week 1 that helped swing the outcomes of fantasy matchups. With that, here are four defenses that could do the same in Week 2.

Seattle Seahawks

The best defense in the NFL in 2025 appeared not to drop their form in the slightest against Drake Maye and the New England Patriots in Week 1. They had three interceptions, which helped in part in them tying for D/ST3 in fantasy football for the week. Now, going into a matchup against a lesser team on paper in Week 2, the Arizona Cardinals, they have a good chance to be one of the better defenses again this week.

The Cardinals in Week 1 had an impressive outing against the Los Angeles Chargers, getting a win and scoring 26 points. Even with that, the way Seattle performed last week and last season makes them a must-start. The Cardinals should still be vulnerable to making mistakes. In five of Jacoby Brissett’s last six games in 2025, he threw an interception.

San Francisco 49ers

In Week 2, the San Francisco 49ers will take on the Miami Dolphins, and from what it looked like in Week 1, Miami could be trending toward being one of the worst teams in the NFL. In their Week 1 matchup against the Las Vegas Raiders, they only scored 13 points. Notably, in 2025, Las Vegas allowed the eighth-most points per game, 25.4.

With the struggles the Dolphins had against the Raiders, fantasy managers with the 49ers defense should lock them into lineups based on what they did in limiting one of the most high-octane offenses in 2025 in their Week 1 matchup against the Los Angeles Rams. They held them to just seven points. That is just the second time in Matthew Stafford’s 85 starts with the Rams that they did not score double digits.

Tampa Bay Buccaneers

The Tampa Bay Buccaneers had a down week defensively in Week 1 against the Cincinnati Bengals. They allowed 33 points. They were still able to be a top-10 fantasy in Week 1, tying for D/ST. That was large in part to them having a defensive TD against Cincinnati.

For Week 2, they should be able to limit their opponent to significantly fewer points, with them facing the Cleveland Browns. In Week 1, the Browns were one of the worst offenses, scoring just 10 points against the Jacksonville Jaguars. In Week 1, in fantasy, the Jaguars finished as D/ST3.

Kansas City Chiefs

The Kansas City Chiefs, despite losing a couple of key defensive players on defense in 2025 were elite in Week 1 against the Denver Broncos. They finished as D/ST6 in fantasy. The Chiefs in Week 2 should be able to continue this level against the Indianapolis Colts. The Colts Week 1 opponent, the Baltimore Ravens, tied for D/ST13 in fantasy last week.

Kansas City is available in most fantasy leagues and is worth the stream play with how they played in Week 1. In ESPN leagues, they are 35.1% rostered.

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