Norwich City and Queens Park Rangers joined Aston Villa on the FA Cup scrapheap after famous wins for non-league Luton Town and third-tier Milton Keynes Dons in the fourth round on Saturday.
Luton, of the fifth-tier Conference National, won 1-0 at Norwich through an 80th-minute Scott Rendell goal to become the first non-league team to eliminate top-flight opposition in 24 years.
League Cup winners in 1988 but relegated from the Football League after going into administration in 2009, Luton began the day 85 places below their opponents in the English league pyramid.
They will be only the seventh non-league team to compete in the fifth round since World War II.
"It's a lot to take in," said Luton manager Paul Buckle.
"The players were tremendous today. They held a Premier League team for 90-plus minutes."
QPR, the Premier League's bottom club, will be able to focus all their efforts on avoiding relegation after a humiliating 4-2 defeat at home to MK Dons of League One.
Although QPR manager Harry Redknapp made nine changes to his team, his starting XI still featured seven full internationals, but they fell behind in the fourth minute when Armand Traore put through his own goal.
Strikes from Ryan Lowe, Ryan Harley and Darren Potter put the visitors 4-0 up by the 56th minute, before Jay Bothroyd and Fabio da Silva claimed a pair of consolation goals for QPR.
Premier League leaders Manchester United enjoyed a much more straightforward fourth-round assignment, sweeping past Fulham 4-1 at Old Trafford to reach the fifth round with ease.
Veteran midfielder Ryan Giggs gave United the lead in the third minute, planting a penalty in the bottom-left corner after Aaron Hughes had been penalised for handball.
United stepped up the pace early in the second period, with Wayne Rooney claiming a neatly taken goal in the 50th minute before a quick-fire Javier Hernandez double put the game to bed.
Hughes replied with a 77th-minute header for Fulham, who welcome United to Craven Cottage in the league next weekend.
Arsenal needed a late Theo Walcott goal to record a 3-2 win at second-tier Brighton and Hove Albion, conquerors of Newcastle United in the previous round.
Olivier Giroud twice gave Arsenal the lead, taking his tally to four goals in two games, but Brighton hit back to equalise on each occasion through headers from Ashley Barnes and Argentine debutant Leonardo Ulloa.
Arsenal had the last word, however, with Walcott netting in the 85th minute to spare Arsene Wenger's men the inconvenience of a replay.