The 24-year old was unstoppable in scoring a hat-trick as Sigi Schmid's men ran Crew ragged, despite them having the third best defensive record prior to the match.
Neagle opened the scoring in just the fourth minute with his first goal at CenturyLink field when he took possession in midfield before advancing into the area and getting his attempt past Will Hesmer, who got both hands to the shot but could not keep it out.
Mauro Rosales struck next from the penalty spot 12 minutes later before Neagle made it 3-0 in the 21st minute when he volleyed home with the inside of his right foot at the back post from James Riley's pinpoint delivery.
Seattle then went four ahead when Mike Fucito grabbed his first goal of the season when he controlled Rosales' pass at the top of the six-yard box before turning and slotting past a hapless Hesmer who had come off his line in an attempt to thwart the effort.
Just prior to the hour-mark, Crew got one back when Jeff Cunningham became Major League Soccers' all-time leading scorer with his 134th goal, coming from the penalty spot, but Columbus' joy was short-lived when Neagle completed his treble in the 70th minute with a rocket from the edge of the area which rasped off the underside off the crossbar.
The scoring for the day was not yet finished as Crew's Josh Gardner made it 5-2 with a brilliant 73rd minute free-kick before the midfielder put the ball into the back of his own net just over a minute later to five the Sounders and easy win.
The Sounders moved to second on the Western Conference table as Crew remained top of the East but were given a very strong message from the Supporters' Shield contenders.
Elsewhere in MLS, Toronto FC and San Jose Earthquakes drew 1-1, Vancouver Whitecaps recorded just their fourth win of the season with a 1-0 home result over Houston Dynamo, Dominic Oduro scored his fourth goal in five games as Chicago Fire beat Colorado Rapids 2-0, FC Dallas came from behind to beat ten man Sporting Kansas City 3-2 away from home and Real Salt Lake overcame the fact they had ten men for more than an hour to win 1-0 at Chivas USA.
2011 MLS season - Week 24 scores
Seattle Sounders: 6 (Lamar Neagle 4'/21'/70', Mauro Rosales (p) 16', Mike Fucito 40', Josh Gardner (og) 74') Columbus Crew: 2 (Jeff Cunningham (p) 59', Josh Gardner 73') CenturyLink Field, Seattle, WA - 36,364
Sporting Kansas City: 2 (Kei Kamara 22', Omar Barvo 68', red card: Teal Bunbury 76') FC Dallas: 3 (Daniel Hernandez 70', Maicon Santos 89', Bobby Warshaw 90+2') LIVESTRONG Sporting Park, Kansas City, KS - 20,018