After an early missed penalty from David Silva, the champions appeared to be on course for another home victory thanks to a goal just before the interval from Carlos Tevez, only for Southampton substitutes Rickie Lambert and Steven Davis to each score within minutes of their introductions.
That sparked a frantic finale which brought back memories of the final day of last season when City scored twice in stoppage-time to beat QPR and win the English title for the first time in 44 years.
They didn't leave it quite that late this time as Edin Dzeko equalised with 18 minutes remaining before France midfielder Nasri struck 10 minutes from full-time to preserve City's unbeaten home run, which now dates back to December 2010.
Nasri's winner eased the anxiety that had been building among City supporters during an entertaining encounter, particularly following an apparently nasty injury suffered by Sergio Aguero in the early stages.
The Argentinian, scorer of the goal that brought City the Premier League title on their last home appearance three months ago, was tackled cleanly by Southampton full-back Nathaniel Clyne, twisting his knee awkwardly as he went to ground.
After lengthy treatment, Aguero was stretchered off, amid natural concerns from players and supporters alike, and the mood around Eastlands was not helped by Silva's appalling penalty miss after 16 minutes.
Tevez, turning onto a neat through ball from Nasri, was clearly tripped by Jos Hooiveld just inside the area, presenting Silva with the perfect opportunity to set City's season rolling.
However, the Spanish midfielder struck a weak shot that was easily saved by goalkeeper Kelvin Davis.
The deadlock was finally broken in the 40th minute. Yet another well-timed through ball from Nasri saw Tevez speed away from his markers, despite a suspicion of offside, and the Argentinian surged into the area before beating Davis at his left-hand post from eight yards.
Dzeko and Tevez were both denied by Davis before the break while, after it, Nasri showed great skill in setting up the unmarked Dzeko, who succeeded only in hitting a weak shot directly into the arms of the goalkeeper.
Gael Clichy and Silva were also guilty of bad misses from close range before Lambert, brought on five minutes earlier, equalised in the 59th minute.
James Ward-Prowse was involved in neat play on the outside of the area and, after Guly Do Prado's shot was blocked by Joleon Lescott, the Saints did well to work the ball back for Lambert to convert with a fine finish from 15 yards.
In the 68th minute the visitors were ahead, via another recently introduced substitute.
After a poor pass from Jack Rodwell, Southampton broke on the counter-attack through Adam Lallana and, after he was stopped in his tracks, he played the ball back for debutant Davis to convert from just inside the City area.
City's response was swift and lethal, within five minutes Vincent Kompany's shot was blocked and, after the effort ricocheted off Yaya Toure, Dzeko had the simple task of sweeping home the loose ball from six yards.
Mario Balotelli missed at the far post, Yaya Toure's fierce free-kick was parried and Dzeko's glancing header flew just wide as City poured forward in search of the winner.
Their pressure finally paid off in the 80th minute. Danny Fox could only weakly head away a far-post cross from Clichy, presenting Nasri with the relatively simple task of converting from 12 yards.
Source: AFP
Source: AFP