Shane Long ended his Premier League goal drought after 35 games, but second-half goals from James McArthur and Luka Milivojevic condemned Southampton to a 2-1 defeat.
Mauricio Pellegrino began the day getting a vote of confidence from Southampton chairman Ralph Krueger, who felt the club had closed the ‘bad’ book following Virgil van Dijk’s sale.
McArthur and Milivojevic, however, spoiled the party, as Palace turned over Southampton after the break with two well-taken goals.
Southampton failed to build on a positive draw at Old Trafford on Saturday, and remains with just one win in the last 12 outings.
Long nearly fired Saints in front after just 15 seconds, but he cleared the bar with his attempt after meeting Dusan Tadic’s knock down.
Tadic then took aim at goal only to send his effort high and over from 20-yards out as Southampton made a furious start to the game.
Pierre Emile-Hojbjerg drew a save from Wayne Hennessey with a thundering effort from distance on 15 minutes, before Long gave Southampton a deserved lead
Long swung his right-foot across Jeremy Pied’s delivery and by Hennessey, who was rooted to the spot.
Crystal Palace made a spirited start to the second-half, as they pressed Southampton back into their own half.
Alex McCarthy denied Christian Benteke from levelling the match after the forward’s shot snuck through traffic in the box on 65 minutes.
McArthur, however, found the equaliser when he smashed in Benteke’s header, which brought Palace’s pressure to a head.
Palace continued to stay in the ascendancy and Milivojevic made it 2-1 to the visitors with a curling effort that had McCarthy beaten from the start.
Southampton: McCarthy, Bertrand, Yoshida (c), Stephens, Pied, Hojbjerg (Gabbiadini 74), Romeu, Ward-Prowse (Davis 70), Tadic (Redmond 79), Boufal, Long.
Unused subs: Forster (GK), Targett, Bednarek, Lemina.
Goals: Long (17).
Crystal Palace: Hennessey, Fosu-Mensah, Kelly, Tomkins, Schlupp (Sako 64), Townsend, McArthur, Milivojevic, Cabaye (c) (van Aanholt 46), Zaha, Benteke.
Unused subs: Speroni (GK), Souare, Delaney, Riedewald, Lee.
Goals: McArthur (69), Milivojevic (80).
Bookings: Fosu-Mensah (57).