The game looked to be heading for a draw until Patrick Bamford poked the ball through the legs of Saints goalkeeper Alex McCarthy to give his side a 73rd-minute lead.
It was Bamford’s 16th goal of the season and does no harm to his chances of securing a place in Gareth Southgate’s England squad for the Euros.
Substitute Tyler Roberts then sealed victory in added time when he tapped the ball into the back of the net.
The victory sees Leeds move above Arsenal and Everton – who both play on Wednesday – and into eighth place.
Leeds’s victory also brought an end to Southampton’s run of home form, which saw them score six goals in wins over Crystal Palace and Fulham.
A marching band welcomed fans into the stadium as the torrential rain turned to sunshine in time for kick-off.
For the first time since December 19 Southampton fans were able to watch their side play in person.
Around 8,000 fans were in attendance, however a few boos rang out among some sections of the Saints faithful before kick-off when the players and officials took the knee.
Leeds goalkeeper Kiko Casilla was called into action early on to deny Che Adams.
Southampton enjoyed the majority of the early pressure, with six shots inside the opening 25 minutes compared to three from Leeds.
It was Casilla who had to make another save before half-time, again from Adams, but neither side were able to find the opener before the break.
The second half started in a similar fashion to the first, with Southampton looking closest to breaking the deadlock.
With a free-kick awarded well within his range, Southampton captain James Ward-Prowse struck the ball well from the edge of the box, only for it to rebound off the woodwork.
Alex McCarthy was then called into action at the other end to parry behind a shot from Stuart Dallas.
Another Southampton move ended with half-time substitute Danny Ings being played in on the edge of the box, the club’s top goalscorer saw his effort fly over the bar.
Leeds finally broke the deadlock when Bamford latched on to Rodrigo’s through ball and finished with the outside of his left foot.
Roberts, who had only come on to the field in the 78th minute, passed the ball into the corner for his side’s second in the fifth minute of added time to secure all three points.
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