First-half action saw the Saints head into the break with a narrow lead and they defended resolutely to hold on to all three points, denting the Blues' hopes of a top-four finish
Saints deservedly went ahead through Jay Rodriguez after a good start to the match, but were pulled back level when John Terry headed home. However a Rickie Lambert free-kick restored the hosts' lead before halftime and they held on for another top-half scalp after the break.
With a gruelling week ahead Rafa Benitez rested a number of key men for the clash, Eden Hazard, David Luiz and Ashley Cole all made way, while Juan Mata (illness) and Gary Cahill (knee) were unavailable. Therefore the likes of Ryan Bertrand, Terry, Marko Marin and Victor Moses started. Saints, meanwhile, were without injured Adam Lallana but young left back and reported Blues target Luke Shaw recovered in time.
The Saints were rewarded for their continued pressure just after the 20-minute mark. Rodriguez received the ball from Lambert in a central position before moving it on to Steven Davis and making a darting run in behind the Chelsea defense. The Scot released it quickly and found the striker, leaving him to slot home past Cech.
Fernando Torres thought he had equalized just moments later when he had the ball in the net after breaking free of Jos Hooiveld, however he was penalized for handling in the build up.
The Blues did get themselves back in the game, however, with just over half-an-hour played. Marin delivered a corner from the right flank which Terry headed home after losing his marker far too easily.
But the clash swayed back in the home side's favor just two minutes later when Bertrand was adjudged to have fouled Davis outside the Blues box. Saints captain Lambert stepped up and smashed the set piece into the top-left corner of the goal, just out of Cech's reach.
Rodriguez called Cech into action once more with a powerful strike from distance but the score remained 2-1 as the halftime whistle was blown.
Clyne forced the Blues keeper into a low save at his near post just after the restart, before denying Marin with a fine challenge, but it was Chelsea which went closest to the next goal as halftime substitute keeper Kelvin Davis did magnificently well to tip over Moses' deflected effort.
Benitez brought Hazard on as he searched for a vital goal and the Blues did indeed pile some pressure on the hosts, as well as having a penalty appeal turned down, but failed to find the cutting edge they needed in the final third.
Lampard failed to emulate Lambert as he flashed a late free-kick over the bar, with Saints able to hold on to a vital victory in their push for survival - also denting Chelsea's hopes of Champions League football next season.