Leicester suffered another home stumble in their bid for Champions League football next season as Southampton erased memories of their 9-0 mauling by the Foxes in October with a 2-1 victory.
Although Dennis Praet scored his first goal for Leicester since his £18million move from Sampdoria in August, a viciously-deflected Stuart Armstrong strike and Danny Ings' 16th goal of the season gave the Saints their fourth Premier League win in five games.
For City, it is now back-to-back league defeats at the King Power Stadium and only one point from a possible nine at home as Brendan Rodgers' side have faltered of late in front of their own fans.
VAR, though, also played a major role in the game, ruling out three offside goals for Leicester, and a penalty decision for the visitors.
Everton continued their improvement under new boss Carlo Ancelotti with a 1-0 home win over Brighton.
Richarlison fired the Toffees in front with a curling finish after 38 minutes.
Brighton went close to an equaliser just before the hour when Leandro Trossard's shot hit the crossbar.
In the 77th minute, Dominic Calvert-Lewin's scrambled goal from an Everton corner was ruled out by VAR for a handball.
Wolves and Newcastle played out a 1-1 draw at Molineux. Miguel Almiron put the visitors ahead after seven minutes. Leander Dendoncker, though, soon equalised following a corner.