The hosts took the lead after seven minutes through Shane Long, which was his first goal since February.
However, Roy Hodgson's Palace showed plenty of determination and their raised effort in the second-half earned them an equaliser through James McCarthur.
The win lifts Palace into 14th place on the Premier League table while Southampton are now truly in a relegation battle as they waver one place above the drop zone.
Speaking after the game, Hodgson commended his players for their attitude in the second-half.
He said: "The players deserve enormous credit to get four points from the program that we've had, with such short recovery time.
"I thought in the first half the pitch was quite heavy and didn't suit the type of football we like to play, but we certainly got over that in second half.
"Today we got the full reward for our efforts and our players deserve enormous credit for their work.
"We knew it would be tough for our midfield, Cabaye we know is a magnificent player but we knew it'd be difficult for him to get 90 minutes so at half time we brought him off and hoped Patrick and Wilfried would lead to more domination in their half.
"Luckily the changes worked for us and I was happy with how it worked out in the end.
"We work hard at our game and set high standards for ourselves. I am demanding, the players are demanding on themselves and we go into every game knowing we aren't beaten.
"We've lost one in 11 which is pretty good by any standard, let alone when you are near the bottom of the table"