David McGoldrick’s 67th minute screamer boosted Southampton`s survival hopes and earned the Saints the three points.
The Saints remain in 23rd place, but the vital win leaves them just two points behind relegation rivals Norwich City, Barnsley and Nottingham Forest.
Manager Mark Wotte made some changes from the side that lost 3-0 at Molinuex on Good Friday, starting Jason Euell and Bradley Wright-Phillips up front, and giving a start to young starlet Adam Lallana.
And it was the hosts who started the brighter, with the hero at Watford on Tuesday night, Jan Paul Saeijs going close with a powerful strike.
Bradley Wright-Phillips then drew a fine save from Speroni and Andrew Surman went close minutes later, and you sensed that the Saints were going to get their first win in eight games.
On 35 minutes, Speroni suffered a facial injury, and captain Clint Hill wore the number 1 jersey while Speroni received treatment off the field.
The St. Mary`s crowd was in full voice and could sense that Southampton could go in 1-0 up at half time with Palace`s left back being in goal.
However, Hill silenced the crowd when he finely denied McGoldrick, when the 21-year-old turned smartly in the box, only for Hill to make a good save with his legs.
One minute before the break, Wright-Phillips was put through by Euell but Speroni, back in the Palace goal, denied the striker with a fine save.
In first half stoppage time Rudi Skacel was put to the floor holding his face, when Rui Fonte elbowed the Saints left back but the Palace player was very lucky to only be given a yellow card by referee Mike Russell.
Both sides emerged from the changing rooms unchanged, and it was again the home side that started brightly, with Jason Euell volleying inches over the bar from an Adam Lallana cross.
After over an hour of Southampton pressure the deadlock was finally broken on 66 minutes and in a spectacular fashion too.
David McGoldrick picked the ball and ran at the Palace defence, and smashed the ball from all of 25 yards and the ball rippled the top right hand corner of Speroni`s goal to send St. Mary`s wild.
Crystal Palace had a late surge with a series of corners, with the Southampton fans nails taking punishment.
The late storm was weathered by the Southampton defence and the three points were rightfully won by Mark Wotte`s men.
Davis, James, Perry, Saeijs, Skacel, Lallana, Wotton, McGoldrick (Liptak 90), Surman, Euell (Saganowski 66), Wright-Phillips (Schneiderlin 77).
Subs Not Used: Forecast, Smith.
Speroni, Clyne, Lawrence, McCarthy, Hill, Comley, Jose Fonte (Hills 76), Carle, Rui Fonte (Stokes 63), Kuqi, Moses (Cadogan 63).
Subs Not Used: Scowcroft, Ertl.