Holders Tottenham will visit Newcastle as they start their defence of the Carling Cup.
Spurs - who beat Chelsea 2-1 to lift the trophy last season - will be looking to claim their first win over the Magpies in six attempts with their last victory in December 2005.
Newcastle, though, needed extra-time to beat Coventry in midweek.
Beaten finalists Chelsea will visit Portsmouth with the south coast club having to endure a tough start to the season.
Pompey have already had to face the Blues and Manchester United and went down 4- 0 to the former in their first game and currently prop up the Barclays Premier League.
Manchester United will host Middlesbrough in ties to be held in the week commencing 22 September.
Arsenal will take on Sheffield United at the Emirates in a repeat of last season's fourth-round clash which the Gunners won at a canter at Bramall Lane on their way to the semi-finals.
It is the third season out of four the clubs have been drawn together in a cup competition.
Everton, who were beaten in the last four by Chelsea, will travel to face Paul Ince's Blackburn.
Liverpool face a seemingly much easier proposition when they host Crewe, who beat Coca-Cola Championship side Bristol City to progress in midweek.
West Ham, with manager Alan Curbishley under severe pressure after his side needed extra time to beat Macclesfield, face a difficult trip to Watford.
Aston Villa host QPR, Fulham - who just squeezed past League One Leicester in midweek - travel to Burnley while Wigan face a tricky tie at Ipswich.
Stoke new boys Ibrahima Sonko and Dave Kitson will face former club Reading when the Royals visit the Britannia Stadium.
Giantkillers Northampton, who knocked out Bolton to reach the third round, are rewarded with a trip to another Premier League side Sunderland.
Should Brighton beat Manchester City in their second-round clash they will fancy their chances against struggling Derby.
Rotherham, who have so far beaten Sheffield Wednesday and Wolves, will host Southampton.
Hartlepool's reward for beating West Brom is a difficult trip to face Leeds, who thumped Crystal Palace in the second round.
Swansea, who also triumphed over Premier League opposition in Hull, will take on local rivals Cardiff.
Arsenal v Sheff Utd
Brighton/ Man City v Derby
Burnley v Fulham
Portsmouth v Chelsea
Blackburn v Everton
Rotherham v Southampton
Swansea v Cardiff
Ipswich v Wigan
Stoke v Reading
Leeds v Hartlepool
Watford v West Ham
Man Utd v Middlesbrough
Liverpool v Crewe
Aston Villa v QPR
Sunderland v Northampton
Newcastle v Tottenham