Andrew Surman and Gregory Vignal scored in the first half to book Southampton's passage into the FA Cup fourth round.
Midfielder Surman grabbed the opening goal for Southampton
Steve Howard twice went close for the Foxes either side of Surman's strike from the edge of the penalty area.
And Vignal crashed home a free-kick from similar distance to put Saints in control, which they never let go of.
Bradley Wright-Phillips almost made it 3-0 and though Howard and Alan Sheehan forced saves from Kelvin Davis, Saints were comfortable winners in the end.
It was the second time in three years that Leicester fell to the same opposition in the Cup and their defeat continues the struggles they have been enduring in the Championship.
New Foxes signing Howard saw an early effort pushed aside by goalkeeper Kelvin Davis but his team went a goal down when Jason Euell laid the ball off to Surman and he found the bottom right corner.
Howard somehow cleared the bar when he connected with Sheehan's inswinging corner and it was 2-0 when Patrick Kisnorbo brought down Grzegorz Rasiak just outside the area, and Vignal slammed the set-piece hard and low past Paul Henderson into the bottom left corner.
Euell and Adam Hammill headed wide after the break, before Howard tested Davis again the Southampton keeper produced a better save to deny Sheehan when he met Iain Hume's cross.
Saints still created the better chances and Wright-Phillips saw an effort kept out by Henderson as they eased home.
Southampton: Davis, Wright, Thomas, Powell, Vignal, Surman, Euell, Safri, Hammill (McGoldrick 85), Wright-Phillips, Rasiak.
Subs Not Used: Bialkowski, Skacel, John, Idiakez.
Booked: Vignal, Safri.
Goals: Surman 16, Vignal 36.
Leicester: Henderson, Stearman, Kisnorbo, McAuley, Sheehan, Kenton (King 46), Fryatt (N'Gotty 46), Wesolowski, Hume, Howard, Hayles.
Subs Not Used: James Chambers, Mattock, Hayes.
Ref: Andy D'Urso (Essex).
BBC Sport Player Rater man of the match: Southampton's Andrew Surman 8.80 (on 90 minutes).
Please note that you can still give the players marks out of 10 on BBC Sport's Player Rater after the match has finished.