Holders Chelsea ended Manchester United's hopes of a first FA Cup win since 2004 and a first double in 14 years as Demba Ba's spectacular strike secured a quarter-final replay victory at Stamford Bridge.
Ba volleyed in a Juan Mata pass four minutes into the second half to send Chelsea into the semi-finals and deny runaway Barclays Premier League leaders United a Wembley clash with derby rivals Manchester City.
Petr Cech made a stunning 61st-minute save from Javier Hernandez and Chelsea held on to stay on course for a fifth FA Cup triumph in seven seasons, with City their last-four opponents on April 14.
Both sides made seven changes for their second game in three days, with Wayne Rooney absent for the visitors after picking up a groin problem on England duty in Montenegro last week. Rio Ferdinand was in the United starting XI, but John Terry and Frank Lampard were only on the bench for Chelsea's second of six games in 16 days.
The opening 20 minutes were even, with United fielding Antonio Valencia at right-back and Phil Jones in midfield, the latter tasked with nullifying the threat of Eden Hazard in particular.
Chelsea were forced into an early change as Ashley Cole pulled up with a hamstring problem as Danny Welbeck rounded him in the 21st minute. Ryan Bertrand came on.
Hernandez, who has been prolific against the Blues with seven goals in 10 games, created space for himself in the area but slipped before he could shoot. Despite the close attention of Jones, the impressive Hazard was Chelsea's most dangerous outlet and he fashioned an opportunity for Ba to shoot, only for David de Gea to save with his feet.
Hernandez had Cech in trouble after 41 minutes. De Gea's long kick found the Mexican, who, with Bertrand standing off, unleashed a swerving 25-yard shot which wrong-footed Cech but the goalkeeper was able to get a firm boot to the ball.
The stalemate was broken four minutes after the re-start when Mata created Ba's fifth Chelsea goal. The Spaniard lofted the ball over the top of the United defence for Ba, who stole in behind Ferdinand to acrobatically volley it over De Gea.
With 29 minutes to go United thought they had equalised when Hernandez met a Welbeck cross, but Cech made a stunning save to palm the ball over. After 88 minutes United again had the opportunity to force extra-time. Ashley Young fed Patrice Evra, who pulled back a cross for substitute Robin van Persie but the Dutchman fired well over as United were left beaten and frustrated.