Making tough lineup decisions each week can be the most challenging part of the fantasy football process. When you're torn between two similar players and simply don't know which to start, start the player with the superior matchup. Week 1 is the toughest week as far as evaluating matchups, as it's commonplace to rely heavily upon the previous year's statistics, even though that ignores how quickly the game changes.

Our matchup rankings provide a schedule-independent method to evaluate positional matchups each week, ranking all 32 opposing defenses in order of most to least favorable for opposing players at all four skill positions. Instead of relying upon seasonal totals, we calibrate points-allowed data to show how each defense fared relative to the difficulty of the schedule it has faced.

Quarterbacks: Baker Mayfield, Tampa Bay Buccaneers (at Cincinnati Bengals), draws an all-around outstanding fantasy matchup. The Bengals finished 2025 the sixth-most-favorable matchup for quarterbacks, and they still have a long way to go. Others to like: Justin Herbert, Los Angeles Chargers (vs. Arizona Cardinals); Kyler Murray, Minnesota Vikings (vs. Green Bay Packers). Matchup to avoid: Patrick Mahomes, Kansas City Chiefs (vs. Denver Broncos), facing one of his worst matchups all season in his first game back.

Running backs: Omarion Hampton, Chargers (vs. Cardinals), is in a situation conducive to a major breakthrough, with limited competition behind him in the banged-up Keaton Mitchell and Kimani Vidal.