Liverpool manager Brendan Rodgers will pit his wits against former club Swansea at Anfield after the holders progressed with a 2-1 win at West Brom.
Bradford City, the only League Two side remaining, must travel to Wigan, while League One Swindon will host Aston Villa, whose reward for winning at Manchester City is a trip to the County Ground.
Neil Warnock's Leeds, fresh from their third round win over Everton, have the chance of claiming another Premier League scalp at Elland Road in the shape of Southampton.
Sunderland will tackle Middlesbrough in a North East derby and there are testing trips for north London duo Tottenham and Arsenal to Premier League rivals Norwich and Reading respectively.
FOURTH ROUND DRAW:
Sunderland v Middlesbrough
Swindon v Aston Villa
Wigan v Bradford City
Leeds v Southampton
Norwich v Tottenham
Liverpool v Swansea
Chelsea v Manchester United
Reading v Arsenal
Ties to be played in the week commencing October 29.