The San Francisco 49ers have the easiest strength of schedule in 2025, with their opponents holding a .415 win percentage from 2024. This advantageous schedule includes matchups against the NFC South and AFC South, as well as games against the Giants, Bears, and Browns. The 49ers are projected to face four rookie quarterbacks, providing a potential boost to their defensive stats.

The New England Patriots also benefit from a favorable schedule, ranking third easiest with a .429 opponent win percentage. This positions them well for a potential playoff push, especially given their last-place schedule advantages.

The Buffalo Bills have the easiest "first-place" schedule, with a .467 opponent win percentage. They are projected to have a 97.8% chance of making the playoffs, with a 35.8% chance of securing the No. 1 seed.

For fantasy football, the 49ers’ easy schedule could enhance the value of their offensive players, such as Christian McCaffrey and Brandon Aiyuk, making them appealing targets in drafts. Conversely, teams like the Detroit Lions, facing the toughest schedule, may see their players face more challenging matchups, potentially impacting their fantasy output.