Goals from Jason Puncheon, Steven Davis and an own goal from Gareth Barry did the damage on a bruising evening for the defending champions on the south coast.
City have won four and drawn two in the 39 days and six games since Yaya Toure departed for the African Cup of Nations.
It’s a period that can hardly qualify as a crisis, yet the narrative has shifted alarmingly since the Ivorian powerhouse signed off for international duty with a key role in that 3-0 New Year’s Day win over Stoke.
Draws against QPR and Liverpool, as well as Manchester United’s ominously efficient assault towards a 20th league triumph left City’s title drive spluttering forward on fumes.
Toure’s return in place of Matija Nastasic was one of two changes from the team that drew against Liverpool, with Samir Nasri also coming back in for James Milner, meaning Javi Garcia dropped back into defence for yet another new central defensive partnership alongside Joleon Lescott.
There was no Carlos Tevez in the squad, missing for personal reasons, meaning that for the first time this season, Roberto Mancini had no striking options on the substitutes bench.
Southampton, under new boss Mauricio Pochettino never conformed to the defensive blueprint favoured by so many sides coming up against the champions and followed Liverpool’s example of attacking City from the first minute.
That attacking impetus earned its reward after just seven minutes.
Puncheon added to his growing portfolio of goals in important games after he reacted first to the loose ball after Joe Hart had deflected a Jay Rodriguez shot away from goal to guide it into the empty net.
City had looked to have gained a foothold in the game over the next 15 minutes but it got even worse when Steven Davis slid home from close range to make it 2-0 after a shot from Lambert was too hot for Hart to handle.
It was an uncharacteristic error from the City stopper that doubled Southampton’s advantage in the same week he was England’s hero with that penalty save from Ronaldinho at Wembley in the week.
City desperately needed a response before half-time and got it after 38 minutes, when Edin Dzeko scored his sixth goal in seven games from six-yards out.
It was a lightning fast breakaway initially spearheaded by the Bosnian hitman and he was on hand to convert Pablo Zabaleta’s cross with an improvised finish as his feet gave way from under him.
There was a penalty scare for the Blues in the second minute of first-half stoppage time but Martin Atkinson adjudged Yaya Toure’s tackle on Rodrigues to be fair, much to the chagrin of the St Mary’s faithful.
In truth, City were second best for long stretches of the first-half and if Dzeko’s goal had offered hope, it was quickly diminished just three minutes after the restart.
The hosts have thrown away 24 points from winning positions this season but they were given a helping hand towards all three points this time when Barry turned a cross into his own net under minimal pressure.
Aguero nearly hit back immediately for the Blues three minutes later with a powerful effort from just inside the penalty area but Boruc was equal to it with strong wrists to turn it away from danger.
Mancini shuffled his pack and brought Milner, Aleksandar Kolarov and Maicon into the fray to try and cancel out the two goal deficit, switching to a three-man defence but Aguero’s effort was as close as City were to come, as the Saints played out the remaining 30 minutes in relative comfort.
It’s the first time that City haven’t won in three games since they reached the nadir of last season’s title race with the 1-0 defeat to Arsenal at the Emirates and the heaviest defeat since April 2011’s loss to Liverpool.
Manchester United go into Sunday’s game with Everton with the chance to extend their lead to 12 points at the table summit.
With just 12 games to go, that could prove to be an unassailable lead.
