Referee Lee Mason adjudicated that Matthew Cash had not handled the ball in the area after Stuart Armstrong’s shot deflected off the defenders thigh on its way towards goal, which was then confirmed by VAR in the 14th minute.
Danny Ings was then denied a late equaliser as he hit the back of the net deep into added time only to be ruled offside by the slightest of margins.
Saints struggled to find the target, however, despite holding the of play as Oriol Romeu and Ryan Bertrand each tried their luck on goal.
Ollie Watkins then had Villa’s first chance on goal on 38 minutes when he held off Jack Stephens before forcing Alex McCarthy into a low save with Jan Bednarek clearing away the rebound.
Four minutes before half-time Villa found the back of the net through Ross Barkley, who fired home Jack Grealish’s cross to make it 1-0 to the visitors.
Things went from bad to worse for an already thin Saints squad after the break with Ibrahima Diallo and Theo Walcott both exiting with injuries within six minutes of one another.
Che Adams had a chance to bring Southampton level, but he was unable to beat Emiliano Martinez 20 minutes from full-time.
It was then late drama avoided for Villa, who saw Bednarek, Stephens and Adams all come close to finding the equaliser only to be denied by last ditch defending.
Martinez pushed aside Bednarek’s header and kept out Stephens either side of John McGinn blocking away Adams.
Ings thought he’d rescued a point for Saints after converting in the 96th minute, but VAR showed he strayed offside by the finest of margins, preserving the Villa lead at the full-time whistle.
Southampton (4-4-2): McCarthy; Bertrand, Stephens, Bednarek, Ward-Prowse; Armstrong, Diallo (Djenepo 59), Romeu (Jankewitz 89), Walcott (Adams 65); Redmond, Ings
Unused subs: Forster (GK), Long, Valery, N’Lundulu, Ramsay, Watts
Bookings: Ward-Prowse (53)
Aston Villa (4-2-3-1): Martinez; Targett, Mings, Konsa, Cash; McGinn, Douglas Luiz; Grealish, Barkley (Nakamba 90+6), Traore; Watkins
Unused subs: Heaton (GK), Taylor, El Mohamady, Trezeguet, Sanson, El-Ghazi, Davis
Goals: Barkley (41)