A stunning Juan Cala strike secured a second Barclays Premier League away victory of the season for the Bluebirds and first in Southampton since October 1962.
Defending resolutely to soak up plenty of Saints pressure throughout, City's Spanish defender stepped up just after the hour mark to bury a left footed effort past Southampton goalkeeper Pablo Gazzaniga in a goal that proved decisive.
With plenty of work left to do City defended to a man to make sure of the win, claiming their first clean sheet since February after another outstanding David Marshall performance. With other results favourable for the Bluebirds, the victory pulls City to within three points of seventeenth placed Norwich City and safety.
Beginning the afternoon with a minute's silence at 3.06pm as a mark of respect for those who lost their lives at Hillsborough 25 years ago, the match started with City attacking the 2.404 away fans who had made the trip to the south coast from South Wales.
Boss Ole Gunnar Solskjær made four changes to the side that lost to Crystal Palace as Fabio, Kim Bo Kyung, Peter Whittingham and Juan Cala all returned to the starting-11 in place of Wilfried Zaha, Ben Turner, Andrew Taylor and Kenwyne Jones.
The Bluebirds' back four was instantly called into action as the returning Cala cleared a low Luke Shaw cross at full stretch. City threatened themselves soon after, the Spanish defenders nod back into the area just evading Mutch and Campbell who could not quite find clean contact to slam the ball home.
The home side were enjoying plenty of possession with their high pressing style earning them much of the ball in the first-half. Gaston Ramirez was soon denied only by the cross bar as his shot deflected from under Steven Caulker only to be denied by the woodwork. Campbell looked to respond, but could only send his headed effort wide.
Marshall was soon at hand before the half hour mark as he parried a Rickie Lambert free-kick away, before ending some good link-up play between the Saints forward and Adam Lallana soon after by stopping the former Bristol Rovers man at the near post.
Three consecutive corners for the Bluebirds saw Peter Whittingham put Gazzaniga under some pressure before the interval, but the scores would be goalless heading into the break.
HALF TIME: Southampton 0-0 Cardiff City
There were no changes for either side at the interval as the Bluebirds once again soaked up pressure from the home side with Saints probing for an opener.
With little in the way of clear cut opportunities however, Mutch made the most of some space on the edge of the area to bring the best from Saints' stopper Gazzaniga who parried his purring effort away. Just a minute later, Saints spurned their best chance of the match as Calum Chambers' cross was headed over by England International Lambert.
Just two minutes later, Ramirez was through on goal after picking up a Jack Cork through ball, only to tumble and fall unopposed as he looked to turn it home allowing Marshall to collect. It proved costly as the Bluebirds took the lead just a minute later.
It came from an unlikely source, as defender Juan Cala made the most of some space on the edge of the box to bury a left footed effort past the Saints' stopper and give City the lead.
With half an hour to see it out, the Bluebirds turned to Scotland's number one to keep their lead in tact. He first denied Saints substitute Sam Gallagher from close range before brilliantly turning a Nathaniel Clyne effort away with less than ten minutes to go.
The travelling 2,404 Cardiff City fans almost had more to cheer as Wilfried Zaha took on an individual counter attack to go one-on-one with the Saints 'keeper, only to be denied by a Gazzaniga save at the last.
The one goal was enough for City however who completed a superb away performance and become only the fifth side the beat the high flying Saints on home turf in the Premier League this season.
FULL TIME: Southampton 0-1 Cardiff City
Cardiff City: Marshall, Caulker (c), Whittingham, Medel (Zaha 61), Campbell, Kim, Mutch, Cala, KTC, Dæhli (Bellamy 86), Fabio (McNaughton 78). Subs not used: Lewis; Turner, Eikrem, Gunnarsson, McNaughton, Zaha, Bellamy.
Goal: Cala (65)
Southampton: Gazzaniga, Chambers (Clyne 67), Fonte, Lovren, Shaw, Cork (Do Prado 78), Schneiderlin, S. Davis, Ramírez (Gallagher 66), Lallana (c), Lambert. Subs not used: Cropper (GK), Clyne, Wanyama, Ward-Prowse, Guly, Hooiveld, Gallagher.
Attendance: 30,526 (2,404 Cardiff City)