Liverpool will host Arsenal and Chelsea face Manchester United in two blockbuster League Cup fourth round ties.
Wednesday's draw for the last 16 produced two eye-catching ties as Jurgen Klopp's Premier League leaders take on the Gunners at Anfield and struggling United head to Stamford Bridge.
Liverpool, who have won the competition a record eight times, beat Milton Keynes Dons 2-0 to reach the fourth round, while Arsenal thrashed Nottingham Forest 5-0.
United, who last won the League Cup in 2017, needed a 5-3 penalty shoot-out victory over third tier Rochdale to limp through after a 1-1 draw at Old Trafford.
In contrast to United's latest disjointed effort, last season's runners-up Chelsea hammered Grimsby 7-1.
Southampton's prize for a first win at local rivals Portsmouth in 35 years is a trip to holders Manchester City.
There were also all-Premier League ties between Everton and Watford and Aston Villa and Wolves.
The two lowest-ranked sides left in the competition, fourth tier pair Crawley and Colchester, were drawn together.
Leicester will travel to Burton, while in an all-League One clash Oxford will host Sunderland.
Fourth round draw
Everton v Watford
Manchester City v Southampton
Crawley v Colchester
Oxford v Sunderland
Aston Villa v Wolves
Burton v Leicester
Chelsea v Manchester United
Liverpool v Arsenal
Ties to be played in the week beginning October 28.