Manchester City piled further misery on struggling Aston Villa with a 4-0 win, adorned by a hat-trick from teenage prospect Kelechi Iheanacho.
Third tier Peterborough United produced the performance of the fourth round when they twice came from behind in the dying minutes to earn a 2-2 draw at Premier League West Bromwich Albion.
On a day when the big guns largely extinguished the hopes of the dreaming underdogs, the League One side proved indomitable after Saido Berahino had twice put Albion ahead.
Peterborough's heroes were Shaquile Coulthirst, who first equalised in the 79th minute, and Jon Taylor, who answered Berahino's second goal with just four minutes left to earn his side a lucrative replay at their London Road home.
Some of the other favourites also earned a fifth-round tie with some comfort.
Tottenham Hotspur accounted for third tier Colchester United 4-1 with a double from Nacer Chadli.
Oxford United, another fourth-tier side, could not repeat their third round giant-killing of Premier League Swansea City as they went down 3-0 at home to Championship Blackburn Rovers.