Two second-half Southampton goals from Joseph Whitmarsh and Princewill Ehibhatiomhan cancelled out City's opener at LCFC Training Ground, which was found just before the interval through Chris Popov.
The new PL2 season dawned for Leicester on home turf in Seagrave as the Saints made the trip to the East Midlands to face a Leicester side which included new summer signing Michael Golding from Chelsea.
It took all of 41 minutes for the deadlock to be broken, which was done by Welsh forward Popov, assisted by Amani Richards, providing the lead for the hosts heading into the break.
Little over the hour mark, the scores were back level again when Whitmarsh was teed up by Derrick Abu, before the same provider set up Ehibhatiomhan for the winner with just over 10 minutes left on the clock.
With game one of the new term concluded, the Foxes quickly switch focus to the EFL Trophy, when they face Burton Albion on Tuesday evening at Pirelli Stadium (7pm BST kick-off); Leicester forming part of Southern Group F with Northampton Town and Notts County also in the group.
The details...
City: French; Cover, Godsmark-Ford, Wilson-Brown (Wormleighton 46'), Ali (Briggs 46'); Raikhy (Ewing 46'), Braybrooke; Richards (Monga 74'), Golding, Marçal; Popov.
Unused sub: Bausor.
Goal: Popov 41'.