Hull City have the opportunity for revenge after being drawn against Arsenal in the FA Cup third round in a repeat of last season's final.
After also being paired together in Monday's rehearsal draw, the Premier League duo will meet at the Emirates Stadium in early January thanks to a curious quirk of fate.
Steve Bruce's men found themselves 2-0 up after just eight minutes in the 2013-14 Cup final at Wembley in May, with defenders James Chester and Curtis Davies getting the goals.
But Arsenal battled back and forced extra-time as Santi Cazorla and Laurent Koscielny drew Arsene Wenger's side level, before Aaron Ramsey netted the winner with 108 minutes on the clock - ending the club's nine-year wait for a trophy.
Three of the five non-league sides left in the competition face the prospect of going head-to-head with Premier League opposition, as Dover Athletic host Crystal Palace, Gateshead visit West Brom and Wrexham travel to Stoke City.
Blyth Spartans, the lowest-ranked club left in the Cup, host Birmingham City, while the final non-league side already through to the third round, Southport, travel to Championship leaders Derby County.
Manchester United will be hosted by the winner of Accrington Stanley and Yeovil Town, while Premier League leaders Chelsea meet Watford at Stamford Bridge.
Meanwhile, Sheffield Wednesday make the trip to Premier League champions Manchester City, Liverpool go to League Two's AFC Wimbledon - almost 27 years after Wimbledon's famous win over the Merseyside club in the 1988 final.
Sunderland entertain Leeds United in a repeat of the 1973 final, and Everton entertain West Ham in one of the four all-top-flight fixtures.
Draw in full:
Arsenal v Hull City
Southampton v Ipswich Town
Stoke City v Wrexham
Charlton Athletic v Blackburn
Dover Athletic v Crystal Palace
AFC Wimbledon v Liverpool
Manchester City v Sheffield Wednesday
Aldershot or Rochdale v Nottingham Forest
West Brom v Gateshead
Blyth Spartans v Birmingham City
Aston Villa v Blackpool
Rotherham v Bournemouth
Huddersfield Town v Reading
Oxford United or Tranmere Rovers v Swansea City
Cardiff City v Colchester United
Bolton Wanderers v Wigan Athletic
Sunderland v Leeds United
Burnley v Tottenham
Derby County v Southport
Brentford v Brighton and Hove Albion
Fulham v Wolves
Leicester City v Newcastle United
Scunthorpe United or Worcester City v Chesterfield
Everton v West Ham United
Cambridge United or Mansfield Town v Bury or Luton Town
Chelsea v Watford
Barnsley or Chester City v Middlesbrough
QPR v Sheffield United
Accrington Stanley or Yeovil Town v Manchester United
Preston North End v Norwich City
Doncaster Rovers v Bristol City