Mebane was selected by the Seattle Seahawks in the 3rd round, 85th overall of the 2007 NFL Draft, and on July 24, he signed a four-year contract. In his rookie season, he played all 16 games and recorded 29 tackles including two sacks. 2008 was a promising year for Mebane as he again played all 16 games and recorded 39 tackles, 5. 5 sacks, and 2 forced fumbles. With the departure of Rocky Bernard, Mebane was expected to make a big impact for the Seahawks in 2009 in which he started 15 games and recorded 49 tackles and 1. 5 sacks. For the 2010 season Mebane started the first four games but suffered a calf injury and was forced to sit out the next four games. In the first four games, he had 8 tackles and 1 sack.