Adam Armstrong scored the decisive goal in the first half, calmly placing the ball into the bottom corner to give Southampton the lead.
Despite pressure from Leeds, including a shot from Daniel James that hit the crossbar, Southampton held on for the victory.
Manager Russell Martin led the Saints back to the top flight in his first season in charge, joining Leicester City and Ipswich Town in the Premier League next season.
Both teams started with unchanged lineups.
Leeds had an early chance with Archie Gray’s shot going wide. Southampton weathered Leeds’ initial attacks, with Will Smallbone’s free kick being their only early threat.
Midway through the first half, Smallbone set up Armstrong, who beat the offside trap and scored from 12 yards out.
Southampton faced a setback when David Brooks left with a shoulder injury, replaced by Sam Edozie. Armstrong nearly scored again before halftime, but his shot was saved by Illan Meslier.
After the break, Leeds had opportunities to equalize. Joe Rodon’s run and pass to Wilfried Gnonto almost resulted in a goal, but Taylor Harwood-Bellis made a crucial block. Crysencio Summerville also came close with a curling shot.
Southampton continued to pose a threat on counter-attacks. Edozie had a chance but missed the target.
In the final stages, Daniel James hit the crossbar again with a volley. During added time, Alex McCarthy saved another shot from James, securing the win for Southampton.
Leeds must now prepare for another season in the Championship, while Southampton celebrate their return to the Premier League.