The Saints have been short of goals for much of the campaign and once again they failed to take chances galore, much to manager Harry Redknapp's frustration.
Hulse, whose ankle was passed fit before the game, missed a heading chance in the opening 48 seconds but rose magnificently to nod Leeds in front after 11 minutes.
Eddie Lewis made a strong run through the middle and was fouled by Matt Oakley. The free-kick was played out to Gary Kelly on the right and Hulse beat everyone in the air to head Kelly's cross into the corner of the net.
It was the prolific Hulse's eighth goal of the season and his 14th in 24 appearances for Leeds who went two up in 19 minutes. This time Hulse was the provider, taking a pass from Shaun Derry with his back to goal and laying the ball off for Robbie Blake to blast his second goal of the season and his first since August 9.
It was typical of the Saints' poor finishing that Theo Walcott failed to beat Neil Sullivan with only the keeper to beat and Ricardo Fuller's shot sped outside a post.
Leeds fans chanted manager Kevin Blackwell's name in response to stories linking Dennis Wise with his job. Wise was not even in the Saints squad, but the Leeds supporters were silenced when a long ball brushed off the head of Leeds defender Paul Butler for Walcott to run clear. Sullivan got his hands to the shot but this time he couldn't prevent it entering the net.
With Nigel Quashie and strikers Walcott and Fuller especially quick off the mark for the Saints, Blackwell replaced Sean Gregan with the younger and faster Matthew Kilgallon in central defence 11 minutes into the second half, after Walcott had squandered another excellent chance.
Walcott took up some excellent positions but his finishing let him down yet again when substitute Kenwyne Jones opened up Leeds' vulnerable defence.