Manneh took advantage of breakdowns in Seattle's back line for goals in the 12th, 42nd and 54th minutes. Vancouver (12-11-9) denied Seattle a chance to clinch the Cascadia Cup the regional rivalry between the Sounders, Whitecaps and Portland Timbers.
Seattle (15-10-6) must win Sunday at Portland to claim regional bragging rights, otherwise it'll go to Vancouver.
The loss was Seattle's first at home since dropping the season opener to Montreal back in March and could be a significant blow to the Sounders' chances of winning the Supporters' Shield for most regular-season points in the league.
Manneh's hat trick was the first for Vancouver since the franchise joined MLS in 2011.
The win also set a franchise mark for most victories in a season (12), but the Whitecaps still trail in the race for one of the final playoff spots in the Western Conference.
Nigel Reo-Coker added his first goal of the season on a counterattack in the 82nd minute as Seattle pushed forward, a shot that went through the arms of Seattle goalkeeper Michael Gspurning.
It marked just the second time Seattle had allowed four goals at home in an MLS match and came after its defense was exposed in a 5-1 loss at Colorado last Saturday.
Clint Dempsey returned from a hamstring injury for Seattle that kept him out since Sept. 13 when he entered in the 51st minute.
Dempsey was left off the U.S. national team for upcoming qualifiers against Jamaica and Panama, while Seattle teammates Eddie Johnson and Brad Evans were called in.
Seattle remained one point behind Real Salt Lake for the top spot in the Western Conference.
Manneh's opening goal came when Seattle defender Jhon Kennedy Hurtado made a poor header clearance right at Vancouver's Diago Kobayashi. Manneh raced past Hurtado, collected the pass from Kobayashi and slid a right-footed shot past Gspurning.
Later in the half, Hurtado and Djimi Traore let Manneh run unmarked and Camilo Sanvezzo's pass found Manneh for his second goal.
Manneh's final goal came on another careless giveaway by Seattle's defense in the opening moments of the second half.
Seattle scored in the 69th minute when Mauro Rosales got his fourth goal of the season off a scramble in the penalty area.
Moments later, Seattle had another scoring chance on a quick counter, but DeAndre Yedlin shot late and Vancouver goalkeeper David Ousted was able to make the save.