Ryan Bertrand’s thumping strike looked to put Southampton on course for a first win of the year, but the hosts quickly unravelled through their own undoing and changed fortunes.
Demarai Gray equalised just four minutes later before Pierre-Emile Hojbjerg compounded matters when he received his second yellow card — for simulation — with less than a quarter hour remaining.
Leicester appeared happy to settle for a draw, but Harry Maguire’s low shot from distance snuck through the crowd and condemned Saints, who has lost 24 points from leading positions since the start of 2017-18, to a crushing defeat.
Southampton took a deserved lead seven minutes after the restart, building upon a first-half that included quality chances from Mohamed Elyounoussi and Danny Ings.
Both drew finger-tip saves from Leicester goalkeeper Kasper Schmeichel, with Ings sending Southampton into the break on the front foot.
Bertrand would provide the opener in the 52nd minute when he smashed an effort from the edge of the box into the top corner to a resounding and relieved reception.
The lead was short-lived and the tension returned as Leicester pulled level through Gray, who capitalised on defending error and fired past a sprawling Alex McCarthy.
Mario Lemina ensured the score remained all-square when he cleared the ball away after Wilfred Nididi’s fizzled cross was mishandled by McCarthy.
Hojbjerg, who was booked early in the game for an accumulation of reckless challenges, then received a second yellow as he foolishly went to ground inside the box.
Southampton hunkered down and felt they could escape with a point only for Maguire to dash those hopes, turning in a low effort from distance in stoppage time.
Southampton: McCarthy, Bertrand, Hoedt, Vestergaard, Cedric, Hojbjerg, Lemina, Elyounoussi (Romeu 80), Redmond, Ings (Austin 70), Long (Armstrong 85).
Unused subs: Gunn, Stephens, Ward-Prowse, Davis.
Goals: Bertrand (52).
Bookings: Hojbjerg (26, 78), Bertrand (64).
Leicester: Schmeichel, Amartey, Morgan, Maguire, Chilwell, Ndidi, Mendy, Gray (Okazaki 88), Maddison (Ghezzal 79), Ricardo, Ihenacho (Albrighton 67).
Unused subs: Ward, Fuchs, Evans, Silva.
Goals: Gray (56), Maguire (90+2).
Bookings: Maguire (90+2).