Leeds had turbulent young striker Alan Smith sent off for a second bookable offence on the hour but by then they were already three goals down.
For Smith it was the ninth dismissal of a troubled career and the second time he had been sent off at Southampton's St Mary's Stadium this season following a red card while playing for England against FYR Macedonia at the same venue.
Southampton would have won by a bigger margin but for some outstanding saves by goalkeeper Paul Robinson.
But there was nothing he could do to stop Southampton taking the lead in the 31st minute when Anders Svensson had a low shot parried by the keeper but the rebound fell nicely for Brett Ormerod to follow up and score.
It was Ormerod's first League goal for six months, in contrast to James Beattie whose goal just before half time was his 23rd of the season.
French winger Fabrice Fernandes centred from the right, Ormerod headed back across goal and Beattie's mis-hit shot deceived the stranded Robinson.
Southampton's third was the best of the match, Beattie breaking away from the halfway line and crossing for Anders Svensson to control before shooting past the keeper.
Smith was booked in the 57th minute for a foul and then an untidy challenge on Michael Svensson resulted in an inevitable dismissal.
Leeds staged something of a comeback in the last ten minutes with Harry Kewell running clear to score before substitute Nicky Barmby added another deep into stoppage time to give Leeds a flattering scoreline.
Smith was not the only Leeds player in trouble. There were also bookings for Danny Mills, Eirik Bakke and Mark Viduka.