He made his professional regular season debut in the Buffalo Bills' season-opener at the New England Patriots and recorded six combined tackles in their 19–17 loss. On October 16, 2006, Williams earned his first career start after surpassing Tim Anderson on the depth chart and made five combined tackles during a 20–17 loss at the Detroit Lions. Defensive coordinator Perry Fewell named Williams the starting defensive tackle for the remainder of the season. In Week 17, he collected a season-high seven combined tackles in the Bills' 19–7 loss at the Baltimore Ravens. He completed his rookie season in 2006 with 53 combined tackles (33 solo) and a pass deflection in 16 games and 11 starts.