Substitute David Connolly and Jose Fonte ended Albion's run of 12 successive home wins after Ashley Barnes gave Gus Poyet's side the lead in first-half stoppage time with his 17th goal of the season following a weak backpass by Radhi Jaidi.
Rickie Lambert headed firmly against the post for Saints before Connolly levelled with a close-range shot after Lambert won a header at the far post. Fonte secured all three points for Saints in the last minute with a superbly directed header at the far post.
Southampton made a bright start and Brighton full-back Marcos Painter was forced to clear off the line following a shot by Brazilian Guly Do Prado in the fourth minute.
Brighton's Danish keeper Casper Ankergren was well positioned to hold a low free-kick from Lambert.
Seagulls' leading marksman Glenn Murray directed a header over five minutes before the break following a cross from the right by Inigo Calderon.