In a marquee match-up between standout quarterbacks and the leading teams in the NFC, Wilson threw for 310 yards and three touchdowns while Drew Brees was unable to make an impact against a dominant Seattle defence.
The red-hot Seahawks (11-1) have now won seven games in a row and not lost at their raucous CenturyLink Field since the 2011 season.
In their latest victory, Wilson almost single-handedly dismantled the Saints defence during the first half as Seattle stormed to a 27-7 advantage by the interval.
The second-year quarterback added 47 of his team's 127 rushing yards while the New Orleans offense struggled to make any sort of headway, with Brees completing a disappointing 23-of-38 passes for just 147 yards and one score.
Following the defeat, the Saints were joined at the top of the NFC South division by the Carolina Panthers (both 9-3) with the teams scheduled to meet in New Orleans on Sunday.