Norwich City FC and Queens Park Rangers FC were eliminated from the FA Cup after losing at home to lower-division opposition, but half a dozen other Premier League teams did progress to the fifth round.
Luton Town FC became the first non-league side since Sutton United FC 24 years ago to defeat a top-flight club in the competition when they won 1-0 at Norwich. Scott Rendell (80) scored the only goal for the Hatters, who started the game 85 places below their hosts in the English football pyramid.
It was also a day to remember for third-tier Milton Keynes Dons FC, 4-2 winners at QPR, whose focus now turns to Premier League survival. In the day's early game, Pablo Zabaleta landed the decisive blow as Manchester City FC prevailed 1-0 away to Stoke City FC in what was a rematch of the 2011 final, which the former also won.
Javier Hernández scored a double as Manchester United FC eased past Fulham FC 4-1 at Old Trafford, while Everton FC triumphed 2-1 at Bolton Wanderers FC courtesy of John Heitinga's late strike and Olivier Giroud was twice on target as Arsenal FC edged Brighton & Hove Albion FC 3-2.
Elsewhere, there wins for Reading FC (4-0) and Wigan Athletic FC (1-0). A full rundown of Saturday's results can be found here.
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