Manchester City, conquerors of Sunderland in the latest final in March, host Sheffield Wednesday, while Liverpool, who have lifted the trophy an unprecedented eight times, entertain Middlesbrough as the seven top-flight teams involved in European competition enter the fray.
Manuel Pellegrini is expected to rotate his star-studded squad as City begin their quest on Wednesday to become only the fourth club to successfully defend the League Cup, following Nottingham Forest, Liverpool and Manchester United.
City thrashed Wigan Athletic and West Ham United 5-0 and 6-0 respectively in their last two League Cup matches at the Etihad Stadium, but their Championship visitors do have reason for optimism.
Wednesday, while a second-tier team, famously upset Manchester United in the 1991 final. They will now attempt to pull off another giantkilling against United's neighbours and they are buoyed by a run of four wins and one draw from their last five away games.
"It's a big game for us and we're not going into it thinking we are beaten already," Wednesday forward Stevie May told the club's official website. "We know it's going to be a tough, tough game but cup upsets do happen, we've seen it many times before. The away support has been a credit to the club and that's a big thing here – the fans are that good."
Middlesbrough, who lifted the trophy in 2003-04, will charge in-form midfielder Grant Leadbitter with ending their 22-game winless run away to Liverpool, who have lost back-to-back matches in the Premier League.
"We've got a massive game in the cup," said Liverpool manager Brendan Rodgers after the latest setback, a 3-1 defeat at West Ham on Saturday. "We need to refocus now and look to get back to winning again."
Arsenal have not won the League Cup since 1993, while Everton, another of English football’s most successful clubs, have curiously never lifted the trophy. Arsene Wenger's men are at home to Southampton on Tuesday, while Roberto Martinez takes his team to 2012-13 winners Swansea City on the same day.
Crystal Palace versus Newcastle United and their under-fire boss Alan Pardew, Sunderland against Stoke City and West Brom hosting Hull City are the other all-Premier League contests.
Sunderland reached last season's final, where they lost to Manchester City, and defender Wes Brown recalled: "It was brilliant, firstly for the fans, for us to get to Wembley. It’ll be a tough game against Stoke, but it's a great competition to be in."
League Cup sponsors Capital One have handed out 1,000 green sweatshirts for Nottingham Forest fans to wear during their game at Tottenham on Wednesday – a gesture to mark the 10-year anniversary of legendary manager Brian Clough's death.
Tottenham and Forest have won the competition four times apiece.
Chelsea, the remaining Premier League team involved, entertain Bolton Wanderers with fringe players Petr Cech, Andre Schurrle, Mohamed Salah, Didier Drogba and Loic Remy all hoping to get the nod to start from Jose Mourinho.
The draw was kind to the last remaining League Two teams. Burton Albion and Shrewbury Town are at home to Championship sides Brighton and Hove Albion and Norwich City respectively.
Cardiff City against Bournemouth and Derby County versus Reading provide all-Championship affairs, while Leyton Orient host Sheffield United and MK Dons face Bradford City in games between League One rivals.
Finally, Fulham - bottom of the Championship - host a Doncaster Rovers team struggling in the division beneath.
