On January 8, 2001, the Buffalo Bills fired head coach Wade Phillips after they finished with an 8–8 record in 2000. Head coach Gregg Williams retained Winfield and Ken Irvin as the starting cornerbacks to begin the regular season. On September 23, 2001, Winfield recorded three combined tackles, a pass deflection, forced a fumble, and intercepted a pass by Colts’ quarterback Peyton Manning during a 42–26 loss at the Indianapolis Colts in Week 2. In Week 14, he collected a season-high eight solo tackles as the Bills loss 12–9 to the New England Patriots. He started in all 16 games in 2001 and recorded 80 combined tackles (68 solo), nine pass deflections, and two interceptions.