Manchester City survived a testing trip to Scunthorpe United, winning 4-2, but Arsenal's defeat meant three of England's big four were out and left Chelsea as clear favourites to retain the famous old trophy.
Defeat was a bitter pill for Arsenal manager Arsene Wenger to swallow as the title-chasing Gunners seek their first silverware since the FA Cup in 2005.
Arsenal, who included 35-year-old Sol Campbell in an otherwise inexperienced lineup against their Premier League rivals, never recovered from Fuller's second-minute opener and despite an equaliser from Denilson they were overpowered.
"It was a good opportunity to win a trophy and we wanted to go through and I think we gave everything," Wenger, who made eight changes to the side that beat Bolton on Wednesday to briefly go top of the Premier League, told the BBC.
"It was a scrappy game but we made a mistake at 1-1 and got caught on a counter-attack. I had not much choice today. It's my responsibility to pick the team and I stand up by that. If it was a mistake it was my mistake."
Stoke celebrated a first ever FA Cup win over Arsenal but manager Tony Pulis's hopes of another home draw were dashed in the fifth-round draw when his side were sent to Manchester City.
Chelsea, who beat Preston North End 2-0 on Saturday, host Cardiff City for a place in the last eight.
YOUTHFUL TEAM
Wenger sent out a youthful team at one of the Premier League's most intimidating grounds with 19-year-olds Craig Eastmond and Jay Emmanuel-Thomas and 18-year-old Francis Coquelin in the starting line-up.
They were shellshocked after two minutes when Stoke's throw-in specialist Rory Delap launched a delivery into the area which evaded the Arsenal defence and reached Fuller who headed past Lucasz Fabianski.
Stoke's bombardment could have brought further goals but Arsenal equalised when Cesc Fabregas lined up a free kick but instead of shooting cut the ball back to Denilson whose low strike deflected into the net just before halftime.
Wenger sent on big guns Eduardo and Andrei Arshavin in the second half but the hosts went back in front 13 minutes from time when Mamady Sidibe galloped down the right wing and his inch-perfect cross gave Fuller the simplest of headers.
Dean Whitehead added the third from Matthew Etherington's low cross.
"This was a very difficult game for us today, make no mistake, irrespective of the team Arsenal put out" Stoke's Pulis said. "Our spirit was fantastic once again. Now my only concern is this week's (Premier League) game against Sunderland.
Manchester City, who play Manchester United in the second leg of their League Cup semi-final on Wednesday, included unsettled Brazil striker Robinho at Championship Scunthorpe and in possibly his last game for the club he scored a dazzling fourth goal.
Roberto Mancini's side made a great start when Martin Petrov put them ahead, only for Paul Hayes to equalise.
Nedum Onuoha edged City 2-1 ahead and Syl
