Rickie Lambert hit two goals to fire Southampton three points clear at the top of the Championship.
Lambert has now hit 87 goals in three years for the Saints and after spending his career in the lower divisions looks set for the top flight.
He opened the scoring before the break with a powerful header from Danny Butterfield's cross.
And he wrapped up the win with a low drive from 20 yards to bring up 30 goals for the season.
With four games to go Nigel Adkins's side are on the brink of back-to-back promotions.
By contrast Palace's season, which has included a run to the Carling Cup semi-finals, is fizzling out after a third straight defeat.
Lambert saw an early shot deflected wide and had a strike disallowed before he did find the net.
Palace old boy Butterfield crossed from the right, defender Paddy McCarthy missed it but Lambert did not, climbing above Nathaniel Clyne to bury his header past Julian Speroni.
Lambert made sure of the win when he was played in by Jack Cork, and after sidestepping McCarthy on the edge of the area he fired a low drive into the far corner.
Southampton boss Nigel Adkins: "I'm pleased with the whole group, although obviously Rickie Lambert scored two very good goals.
"We have played some really good football this season, we create opportunities and we need someone to put the ball in the net.
"He's a talented, talented football player and he's at a good place. Southampton has a great culture and is a great place for a player to become the best they can be.
"He's going from strength to strength and he's reaping rewards for his hard work this season."
"Rickie Lambert was the difference.
Crystal Palace boss Dougie Freedman: "He has experience and if I was a betting man I'd say he'll produce a few goals in the Premier League.
"The first goal was against the run of play and was a bitter pill to swallow.
"But I'm very happy with our performance. We gave it a right good go with six youngsters against a top team."