Saints lost out in a thrilling 3-2 defeat to Manchester United at Wembley in February last season despite Marco Gabbiadini's double.
Lancashire rivals Blackburn and Burnley will renew acquaintances at Ewood Park in a fixture playfully dubbed locally as 'T'el Clasico', with their last meeting having coming in the Championship during the 2015-16 season, with the Clarets running out 1-0 victors on that occasion.
Elsewhere, Leicester City are away to Sheffield United, Newcastle United host Nottingham Forest, while West Ham were drawn at home to Cheltenham Town, although they will play the match away because the London Stadium will not be ready after the IAAF World Championships.
Crystal Palace face a home tie with Ipswich Town and West Brom are on the road against Accrington Stanley. Stoke City are set to play Rochdale at bet365 Stadium, Swansea City will travel to play MK Dons, while Watford host Bristol City.
The teams that progress from the 25 ties and move into the third round will be joined by England's seven representatives playing in Europe this season.
Carabao Cup (@Carabao_Cup) August 10, 2017
Ties will be played on the week commencing August 21.