Carabao Cup holders Manchester City will be away at Preston when they make their bow in the competition this year.
Champions League winners Liverpool will travel to MK Dons and another League One side, Rochdale, can look forward to a trip to Old Trafford to face Manchester United.
League Two Colchester upset Crystal Palace on penalties on Tuesday and have been rewarded with a tie at home to Tottenham.
Crawley upset Norwich on Tuesday night and their reward is a home game against Championship Stoke.
Chelsea - who lost on penalties in last year's final - have home advantage against Grimsby or Macclesfield, whose second-round game was abandoned due to a waterlogged pitch.
There will be a south-coast derby at Fratton Park between League One Portsmouth and Premier League side Southampton.
Pompey won 2-0 at Championship QPR on Wednesday and assistant manager Joe Gallen said of the draw: "It's great.
"I really love derby games and I think it's brilliant that we're now going to play Southampton."
Brighton will host Aston Villa in an all-Premier League tie, West Ham face a potentially tricky trip to League One Oxford, while Bournemouth play last season's semi-finalists Burton, Leicester visit Luton and Everton travel to Sheffield Wednesday.
Arsenal host Nottingham Forest, Wolves entertain Reading, Swansea visit Watford and Sheffield United meet Sunderland at Bramall Lane.
Wolves vs Reading
Oxford vs West Ham
Watford vs Swansea
Brighton vs Aston Villa
Sheffield United vs Sunderland
Colchester vs Tottenham
Portsmouth vs Southampton
Burton vs Bournemouth
Preston North End vs Manchester City
MK Dons vs Liverpool
Manchester United vs Rochdale
Luton vs Leicester City
Chelsea vs Grimsby or Macclesfield
Sheffield Wednesday vs Everton
Arsenal vs Nottingham Forest
Crawley Town vs Stoke City
(Ties will be played in the week commencing September 23.)