Striker Armando Broja, on loan from Chelsea, scored the winning goal on his first Premier League start to secure all three points for Saints.
The winning goal came during a rare moment of Leeds pressure around the Southampton penalty area.
After an attack broke down, the ball fell to Moussa Djenepo who expertly slid a pass to a charging Nathan Redmond to start a blistering counter attack.
Redmond displayed both his pace and awareness after carrying the ball and squaring it to the advancing Broja to slam home what would turn out to be the game’s winning goal.
“It was amazing to get my first start in the Premier League, I’ve been dreaming of this moment since I was three years old,” Broja said after the game.
“Scoring on my first start is a dream come true, I couldn’t ask for anything better. This is the favourite moment of my career so far, hopefully there are many moments and goals more to come.”
Broja, who was born in Slough to Albanian parents and recently scored a big goal for the country in the last round of World Cup qualifiers, thanked Redmond for his work for the goal.
“It was a great run from Nathan Redmond, he said before the game the goals will come, just to keep making runs. He put the ball on a plate for me and I was able to finish.”
Despite missing Che Adams through injury and captain James Ward-Prowse through suspension, Southampton looked the stronger team throughout the 90+ minutes at St Mary’s.
In the first half, a number of good-quality chances came from Redmond’s deliveries from corners. Broja went close to scoring with a flicked-on header and Mohamed Elyounoussi also scored the opener with a diving header at the far post.
Leeds, who were missing key players such as Kalvin Phillips, Patrick Bamford and Raphinha, never really got going.
Saints’ two defensive-minded pairings in the centre of the park in Jan Bednarek and Mohammed Salisu, and Oriol Romeu and Ibrahima Diallo did well to limit Leeds to just two shots all game.
On top of the long-awaited three points, more good news for Saints fans came in the form of Stuart Armstrong.
The Scotland international made his first appearance for Southampton this season as a substitute, picking up his first minutes since recovering from a calf injury.
Southampton (4-4-2): McCarthy; Livramento, Bednarek, Salisu, Perraud; Elyounoussi (Tella 95’), Diallo, Romeu, Djenepo (S. Armstrong 59’); Broja (Walcott 81’), Redmond
Unused subs: Forster, Lyanco, Walker-Peters, A. Armstrong, Long, Valery
Goals: Broja (53’)
Bookings: McCarthy, Bednarek
Leeds United (3-4-3): Meslier; Llorente, Struijk, Cooper; Klich (Gelhardt 77’), Shackleton, Dallas, Roberts (Summerville 81’); Harrison, Rodrigo (Forshaw 64’), James
Unused subs: Klaesson, Hjelde, Cresswell, Dramaeh, McKinstry, Greenwood
Bookings: Llorente, Struijk, Roberts