Like Liverpool, beaten at home by Wolverhampton Wanderers the previous day, they miscalculated in resting so many players ahead of league games in midweek and could have no complaints at going out of the competition.
Watford lost 1-0 to League One (third tier) side Millwall and on the other side of London, Hull, FA Cup finalists three years ago, were humbled 4-1 by Championship (second tier) side Fulham after missing two late penalties.
Leeds, fourth in the Championship and giving greater priority to returning to the Premier League after a 13-year absence, lost 1-0 to Sutton United, who joined fellow fifth-tier National League club Lincoln City in the last 16.
Millwall, who beat another understrength Premier League team, Bournemouth, in the previous round, fully deserved the win earned for them with a goal by Steve Morison in the 85th minute.
The 33-year-old striker, in his second spell with the London club, drove in a cross to the far post by substitute Shane Ferguson.
Watford’s manager Walter Mazzarri made seven changes, including experienced players like captain Troy Deeney, and midfielders Etienne Capoue and Tom Cleverley among the substitutes.
Without joint top scorers Deeney and Capoue, they struggled to make genuine chances, coming close only when a free kick by Adlene Guedioura was glanced against the far post by Millwall defender Shaun Cummings.
They also failed to convince the referee about two strong penalty appeals either side of halftime, and in between times lost goalkeeper Costel Pantilimon to injury.
Brazilian former Tottenham Hotspur keeper Heurelho Gomes came on and immediately had to make an excellent save from a volley by striker Lee Gregory, who had hit the bar in the first minute.
“We’re a good honest bunch who work hard,” goalscorer Morison told the BBC.
Manager Neil Harris felt his mid-table League One team fully deserved their victory over a side 40 places above them.
“We could easily have been three or four up by halftime,” he said.
“This club and this team epitomise what the FA Cup is all about.”
At Craven Cottage on the bank of the River Thames, Hull, who had made six changes, fell behind to a goal by their former forward Sone Aluko after 16 minutes.
Evandro headed an equaliser four minutes into the second half, but Chris Martin, on loan from Derby County, soon restored the lead.
Promising youngster Ryan Sessegnon added a third goal and
with 12 minutes left Stefan Johansen scored a fourth.
Hull’s Abel Hernandez then had two penalties saved by goalkeeper Marcus Bettinelli in the space of a minute to round off a bad day.
Former European Cup finalists Leeds, out of the top flight of English football since 2004, fielded almost a complete reserve team on the artificial pitch at Sutton and found the non-Leaguers, 84 places below them, too strong.
Captain Jamie Collins scored the only goal from a penalty after 53 minutes and Leeds finished with only 10 men when their own captain, Liam Cooper, was sent off near the end for receiving a second yellow card.
(Reporting by Steve Tongue; Editing by Toby Davis)