Jacksonville Jaguars defensive end Wesley Williams (90) is celebrated for his fumble recovery during the second quarter of an NFL preseason football matchup at EverBank Stadum on Friday, Aug. 28, 2026 in Jacksonville, Fla. [Corey Perrine/Florida Times-Union]

Defenses, although they are among the last selections in fantasy drafts, have the potential to flip fantasy matchups. With that, here are four must-start defenses that could do just that in Week 1.

The Los Angeles Chargers are playing one of the worst teams in the NFL in 2025: the Arizona Cardinals. They will be trotting out QB Jacoby Brissett as their Week 1 starter. While he had flashes of good production in his time on the field last season, it was still evident that turnovers can be an issue for him.

In 2025, Brissett threw an interception in five of his last six games. With that, the Chargers should generate turnovers against Arizona, especially through the air. Los Angeles in 2025 was tied for the third-most interceptions in the NFL with 19. The Cardinals may also be forced to use their pass game more than they usually would, with RB Jeremiyah Love’s status up in the air for Week 1. He is currently recovering from a high ankle sprain.

The Jacksonville Jaguars play the Cleveland Browns in Week 1. That alone makes them a must-start defense. In 2025, the Browns averaged the third-fewest yards per game in the NFL, 262.1. They also averaged 1.1 interceptions per game last season, which was the third-highest average in the league.

The Browns did make changes to their offense, adding promising rookie WRs KC Concepcion and Dezel Boston, and will have a different starter at QB with Deshaun Watson. But with it being the two WRs' first NFL game, and Watson struggling in his tenure with the Browns as a whole and in the preseason, it could be a spell for disaster against a veteran defense.

The Philadelphia Eagles will be taking on the Washington Commanders in Week 1, and despite them having one of the more dynamic QBs in the NFL with Jayden Daniels, they should struggle in Week 1 against Philadelphia.

The Commanders are bringing in a few offensive starters into the fold who were not on their 2025 team—WR Stefon Diggs, RB Rachaad White, and TE Chig Okonkwo. Getting them fully adapted to Washington’s system could take a few weeks before everything clicks.

Philadelphia should capitalize on the Commanders' inexperience as a group. The Eagles are also coming into the 2026 season in good form. From Weeks 14-18, they were DST2 in fantasy football.

With the recent announcement of Tua Tagovailoa being the Atlanta Falcons' starting QB, the Pittsburgh Steelers, who were already one of the higher-level fantasy defenses coming into the 2026 season, get a slight boost in their value for Week 1 against Atlanta.

Tagovailoa in 2025 was flat-out bad for the Miami Dolphins. He threw the second-most interceptions in the NFL with 15, only trailing Geno Smith, who threw 17. This is certainly a weakness that the Steelers can jump on. In 2025, they were tied for the eighth-most interceptions in the NFL with 15.