Liverpool's 44-match unbeaten streak in the Premier League ended in stunning fashion with a 3-0 defeat at Watford on Saturday and they were rocked again at Stamford Bridge.
Keeper Adrian, in for the rested Alisson, endured a horrible moment when he allowed Willian's powerful shot to bounce off him and into the net in 13th minute.
To complete a miserable night for Liverpool, former Everton midfielder Barkley drove home Chelsea's second goal just past the hour mark after a surging run.
Eight-time winners Chelsea thoroughly deserved their win and manager Frank Lampard will take heart from the fact that on the last two occasions they have beaten Liverpool in the Cup they have gone on to lift the trophy.
"They are the best team in the land, this year what they are doing in the league is incredible," Lampard said.
"So for us to put in the effort, focus, determination and quality was something special tonight. It's a one-off I know, but you have to celebrate these moments."
After having their dream of an unbeaten season wrecked at Watford, Liverpool's manager Juergen Klopp made seven changes but still started with Virgil van Dijk, Sadio Mane, Joe Gomez, Andy Robertson and Fabinho -- a far cry from the previous round at Shrewsbury when he fielded a virtual under-21 side.
It was clear from the start that Klopp wanted an immediate response to the Watford shocker, and he almost got it with Mane failing to capitalise on a golden early chance.
A frenetic opening saw Adrian make a stunning save from Willian but seconds later he went from hero to villain.
Fabinho was caught in possession and Willian let fly again. The shot went straight at the keeper but it somehow squirmed past him and into the back of the net.
At the other end, Chelsea keeper Kepa Arrizabalaga, back for the first time since being dropped in January, made a remarkable triple save before halftime.
Liverpool faded in the second half and when Barkley burst forward and fired past Adrian the game was as good as over.
Chelsea fans delighted in a superb display by 18-year-old Billy Gilmour in midfield on only his third start for the club.
For Liverpool, a season of utter dominance which will almost certainly deliver a first league title for 30 years, has suddenly hit the buffers. They have been beaten three times in four games in all competitions having also lost to Atletico Madrid in the first leg of their Champions League, last-16 tie.
"We deserved to lose because they scored twice and we made massive mistakes for both goals," Klopp said.
"Nobody has to feel sorry for us, we will win football games and that is what we want to do on Saturday."