John bagged the only goal after just 15 minutes to hand Saints a third win in four matches and condemn misfiring Cardiff City to their first away loss of the season.
Trinidad & Tobago international John picked out the bottom left corner of Michael Oakes' goal with a clinical first-time shot after Spaniard Inigo Idiakez had carved open the Bluebirds defence.
Cardiff's veteran strike duo Robbie Fowler and Jimmy Floyd Hasselbaink went on to endure a frustrating afternoon on the South Coast.
Fowler felt he should have had a penalty inside the opening 50 seconds when he was tugged back by Alexander Ostlund, but referee Alan Wiley waved away the appeals.
Hasselbaink should have equalised two minutes before half-time after combining well with Fowler, only to shoot into the sidenetting.
Southampton goalkeeper Kelvin Davis denied Hasselbaink three minutes after the restart when he parried away the Dutchman's long-range drive.
Fowler must have thought he had broken Saints' resistance four minutes later, but he made a mess of his close-range header, allowing Jhon Viafara to clear off the line.
Southampton came into the game with the worst defensive record across the four divisions and were given a torrid time by the visitors' attack.
Substitute Peter Whitingham should have made the pressure tell in second half stoppage time when he was played in by Trevor Sinclair, but scuffed wide with only the stranded Davis to beat.
There was still time for one last Bluebirds attack and Fowler looked certain to equalise from close range, before a heroic block from Southampton's on-loan Reading defender Alan Bennett.
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