Wigan's prolific forward Nathan Ellington netted both their goals as the division two leaders saw off visiting Fulham 2-1 to claim their third premier league scalp of the competition.
Chelsea striker Jimmy Floyd Hasselbaink scored twice and Everton's teenage sensation Wayne Rooney had a penalty saved in a one-sided all-premier league clash at Stamford Bridge.
Chelsea, semi-finalists last season, will now play Manchester United at Old Trafford, where they have a good record, in the pick of the quarter-final ties.
Liverpool won a penalty shootout 5-4, with Senegal striker El Hadji Diouf scoring the decisive spot kick, after being held 1-1 by first division Ipswich at Anfield.
Holders Blackburn Rovers crushed first division Rotherham United 4-0 and Aston Villa were untroubled by first division Preston North End, romping to a 5-0 win at Villa Park.
Wigan held on against Fulham to add to their wins over Manchester City and West Bromwich Albion and claim a place in the quarter-finals for the first time in their history.
Cup specialist Ellington, scorer of a hat-trick against West Brom, grabbed two first half goals, after 20 and 28 minutes, to put Wigan in command against a lacklustre Fulham.
Portuguese forward Luis Boa Morte pulled one back with four minutes left but it was too late for the Londoners.
MASTERLY ZOLA
Gianfranco Zola was the architect of Chelsea's victory at Stamford Bridge.
The Italian master's curling pass set up Hasselbaink for the home side's first after 26 minutes and a minute before the break Zola's expert chip allowed Emmanuel Petit to volley in the second.
Croatian midfielder Mario Stanic and Hasselbaink,
Everton's woes were compounded when Rooney's ill-placed spot kick was well saved by Chelsea keeper Carlo Cudicini.
Gary Naysmith's close range goal soon after was scant consolation for David Moyes's side, who have now lost twice in succession having won their previous seven matches.
They will, however, get the chance to avenge the loss when the two teams meet at Goodison Park in a premier league fixture on Saturday.
Misfiring Liverpool surprisingly fielded Polish goalkeeper Jerzy Dudek, guilty of a terrible error in Sunday's 2-1 defeat by Manchester United, from the start against Ipswich.
But within 14 minutes Dudek was picking the ball out of his net after Tommy Miller profited from poor defending to give the visitors a shock lead.
Liverpool, the 2001 League Cup winners, hauled themselves level when youngster Neil Mellor was fouled after 54 minutes and Diouf struck home the penalty.
Extra-time proved fruitless and in the penalty shootout, after Ipswich's Jamie Clapham missed, Diouf held his nerve again to seal a quarter-final tie at Villa.
YORKE DOUBLE
Wigan next face Blackburn, whose strikers Dwight Yorke and Andy Cole gave manager Graeme Souness the response he was seeking against Rotherham after the signing of Turkish forward Hakan Sukur earlier on Wednesday.
Yorke grabbed two goals and Cole one in a dominant opening by the holders and Damien Duff added a fourth before halftime to render the second half a formality at Ewood Park.
England striker Darius Vassell rediscovered his goalscoring touch with well-taken goals after 44 and 55 minutes at Villa Park against Preston.
Second-half strikes by Dion Dublin, Juan Pablo Angel and Thomas Hitzlsperger completed Villa's comprehensive win.
