The home side dominated possession throughout Saturday's contest at St Mary's, and could easily have gone in at half-time with the lead after Gaston Ramirez hit the crossbar.
Paulo Gazzaniga in the Southampton goal was rarely called into action, but was beaten 20 minutes into the second half as Cala found the net from 20 yards.
Cardiff goalkeeper David Marshall made a pair of important saves late on to safeguard the visitors' lead.
With Fulham picking up a 1-0 victory against Norwich City, and bottom-placed Sunderland losing by the same scoreline to Everton, the result - Cardiff's second away league win of the season - lifts Ole Gunnar Solskjaer's side to within three points of safety and opens up the battle for survival.
Cardiff will have been especially careful to keep their starting XI under wraps after the spying scandal that followed their 3-0 home defeat to Crystal Palace last weekend, while Southampton brought Ramirez in for the injured Jay Rodriguez.
Information leaks have dominated headlines off the field in south Wales, but it is Solskjaer's porous defence that has caused most problems on it in recent weeks - conceding 12 goals in their previous three fixtures - and it was not long before they were put to the test on the south coast.
Steven Davis dragged an effort across the face of goal after 14 minutes, before Adam Lallana's low drive was comfortably collected by Marshall.
Ramirez then had the visitors' crossbar rattling with a deflected effort from inside the penalty area.
Cardiff were struggling to get any kind of foothold in the game against a Southampton side with little to play for.
Rickie Lambert forced Marshall into a diving save from a 20-yard free-kick after 27 minutes, and the hosts had calls for a penalty turned down before the break - referee Jon Moss waving away claims of handball against Steven Caulker.
The second half continued in the same vein as the first, with Southampton dominating possession, but Gazzaniga was forced into action just before the hour mark as he punched clear a Jordon Mutch effort from distance.
And, having looked incapable of finding a way through the home defence for the opening hour of the match, Cardiff took the lead in the 65th minute - Cala firing home a left-footed strike from 20 yards after Southampton failed to clear their lines from a free-kick.
Marshall denied substitute Sam Gallagher and Nathaniel Clyne superbly in the closing stages as Cardiff clung on for a vital three points and gave Mauricio Pochettino a day to forget in his 50th Premier League match in charge of Southampton.
