Non-league Luton Town pulled off an historic FA Cup upset by winning 1-0 at Premier League Norwich City in the fourth round on Saturday, while third-tier Milton Keynes Dons humbled Queens Park Rangers 4-2.
Luton, of the fifth-tier Conference National, prevailed through an 80th-minute Scott Rendell goal at Carrow Road 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.
QPR, the Premier League's bottom club, can now focus all their efforts on avoiding relegation after a humiliating 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 Dean Lewington stabbed in at a corner.
Ryan Lowe made it 2-0 five minutes before half-time and then set up Ryan Harley early in the second half, before Darren Potter added a fourth in the 56th minute when QPR failed to clear a corner.
Jay Bothroyd and Fabio da Silva claimed a pair of consolation goals for QPR.
Arsenal overcame stubborn resistance from second-tier Brighton and Hove Albion, conquerors of Newcastle United in the previous round, to reach the fifth round with a 3-2 win.
Olivier Giroud found the top-left corner to put Arsenal ahead in the 16th minute but Brighton drew level in the 33rd minute when Ashley Barnes beat visiting goalkeeper Wojciech Szczesny to a right-wing corner.
Giroud restored Arsenal's lead 11 minutes into the second half, bringing down Abou Diaby's pass and finishing sharply, but again Brighton replied, with Argentine debutant Leonardo Ulloa stooping to head home Barnes' sweeping cross.
Arsenal had the last word, however, with Theo Walcott netting in the 85th minute to spare Arsene Wenger's men the inconvenience of a replay.
Everton, fifth in the Premier League, needed an injury-time winner from John Heitinga to prevail 2-1 at second-tier Bolton Wanderers.
South African midfielder Steven Pienaar had diverted a Victor Anichebe shot into the net to put the visitors ahead in the 18th minute, only for Marvin Sordell to equalise nine minutes later.
Luton's fellow fifth-tier representatives Macclesfield Town were knocked out, going down 1-0 at home to Wigan Athletic courtesy of a seventh-minute Jordi Gomez penalty.
Earlier, a late goal by Pablo Zabaleta earned Manchester City a 1-0 win in an attritional tie at bogey team Stoke City.
The English champions had not won at Stoke in six previous visits and they lost captain and centre-back Vincent Kompany to an ankle injury in the first half.
However, Zabaleta struck in the 85th minute to send Roberto Mancini's men into round five, finishing deftly from Sergio Aguero's low cross to complete a move that he had started.
"Today we were solid at the back, and up front we were very aggressive," said Zabaleta, an FA Cup winner with City in 2011.
"The Stoke crowd push the team a lot and we knew it was going to be difficult for us. We want to win the FA Cup again."
Premier League leaders Manchester United are in action in the evening kick-off, with top-flight rivals Fulham the visitors to Old Trafford.
The fourth round began with an upset on Friday, when Aston Villa, beaten by fourth-tier Bradford City in the League Cup in mid-week, lost 2-1 at Championship club Millwall.