Southampton's miserable home form continued as Peter Crouch struck the only goal of the game to help Stoke to a first away win since January on the final day of the season.
The home side enjoyed the majority of possession but Nathan Redmond's lob on to the bar on the stroke of half-time was their best moment until Crouch pounced.
The striker's 10th goal of the season arrived when he headed home a Geoff Cameron cross and they deserved the lead after creating openings throughout.
Southampton rallied late on as Jack Butland produced fine saves to deny Steven Davis, James Ward-Prowse and Sofiane Boufal but Claude Puel's side end the campaign without a win in five games at St Mary's.