The largest shut-out in NFL history occurred on October 10, 1920. The Rochester Jeffersons beat Fort Porter, 66-0. The Seattle Seahawks shut-out the Arizona Cardinals, 58-0, on December 9, 2012.
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In the 1989 season opener between the Pittsburg Steelers and Cleveland Brown's, at Three Rivers, the Browns crushed the Steelers 51-0. I'm not sure if this is the biggest regular season deficit in NFL history, but it certainly stands as the worst shut-out in the Super Bowl era.
The most lopsided shutout in NFL history was when the Chicago Bears defeated the Washington Redskins 73-0 in the 1940 NFL Championship game.
Regular Season: Philadelphia Eagles beat Cincinnati Reds 64-0 on November 6th 1934. NFL History: Chicago Bears defeated the Washington Redskins, 73-0, in the 1940 NFL Championship game.
The 1940 NFL Championship where the Chicago Bears beat the Washington Redskins 73-0.