The playoff-bound Seahawks intercepted Giants quarterback Eli Manning five times and took another step toward securing the National Conference post-season top seed.
Richard Sherman and Byron Maxwell had two interceptions apiece and the Seahawks limited the Giants to 181 total yards in what New York coach Tom Coughlin called "a pathetic offensive performance".
"It felt great to us," Seahawks safety Earl Thomas said. "The biggest thing is how much fun we had. Guys were out there playing free like it was backyard football."
It was the first time in 18 years that the Giants were shut out at home.
The venue took on even more significance since it is where the Super Bowl will be held on February 2, in what promises to be a chilling climax to the NFL season.
Marshawn Lynch added 120 yards from scrimmage and a touchdown for the Seahawks, who went into the contest one game in front of New Orleans in the race for home field advantage.
The Saints stumbled on Sunday in a 27-16 loss to the St Louis Rams.
The Green Bay Packers kept their playoff hopes alive as they matched the biggest comeback in club history in erasing a 23-point halftime deficit to edge Dallas 37-36.
Eddie Lacy's one-yard touchdown plunge with 1:31 to play completed the Packers' epic comeback, achieved with starting quarterback Aaron Rodgers still sidelined by a broken collarbone.
With back-up Matt Flynn guiding the offense, the Packers scored touchdowns on their first five possessions of the second half.
Cowboys quarterback Tony Romo, meanwhile, threw interceptions on Dallas' last two possessions.
The Cowboys remained a game behind NFC East division leaders Philadelphia, who fell 48-30 to Minnesota.
The Kansas City Chiefs locked up their playoff spot with a 56-31 victory over Oakland.
The Miami Dolphins boosted their bid for an American Conference wild card spot with a 24-20 upset of the New England Patriots.
New England missed a chance to clinch the AFC East crown and opened the door for Denver to claim the top seed in the conference.
Jay Cutler returned for Chicago after four games sidelined by injury and led the Bears to a key 38-31 victory at Cleveland.
The Bears are a half-game ahead of Detroit atop the NFC North.
AFC South division winners Indianapolis rebounded from a loss at Cincinnati last week with a 25-3 victory over the reeling Houston Texans.
In other games, San Francisco moved closer to a playoff berth with a 33-14 win over Tampa Bay, Atlanta edged Washington 27-26, and Buffalo beat Jacksonville 27-20.
In Pittsburgh, Antonio Brown had a receiving touchdown and returned a punt for a score to lead the Steelers to a 30- 20 win over Cincinnati, who lead the AFC North.