Omar Rowe drilled home from 12 yards out to give Saints a 1-0 advantage seven minutes before the interval.
Kevin Toner's own-goal doubled Saints lead, before Daniel Johnson brought Villa back into the game.
Defender Jordan Turnbull headed in Saints third towards the end, ensuring Saints continued to progress up the table.
The game began at a frantic pace, and Villa 'keeper Benjamin Siegrist was perhaps lucky to stay on the field after four minutes.
He came out of his area to close down Tadanari Lee's shot, which struck the stopper's outstretched hand. The referee awarded Saints a free-kick but only showed a yellow card to Villa’s shot stopper.
From the resulting free-kick, Lee’s low effort was parried away as far as defender Jason McCarthy, who could only strike the ball back at Siegrist, who turned it over the bar.
Rowe was next to test Siegrist, as his left-footed shot was turned around the post.
Villa grew into the game after that tough opening, although Andreas Stiber’s long-range effort didn’t trouble Saints goalkeeper Chris Johns.
Saints had the ball in the net after 21 minutes, when Rowe’s free-kick was flicked home by Jordan Turnbull – however the referee adjudged a foul had been committed off the ball.
Both sides kept the ball well in the middle of the park, but it was Saints who looked the more dangerous as Jake Sinclair twice whipped in crosses that evaded Barnard.
But, on 38 minutes, Saints deservedly made the breakthrough. This time Sinclair’s cross was inch perfect for ROWE, who chested the ball down before drilling past the goalkeeper for 1-0.
Lee then had a low effort deflected wide before the interval, as Saints ended the half on top.
HALF TIME: SOUTHAMPTON U21S 1-0 ASTON VILLA U21S
It took seven second-half minutes for Saints Under-21s to double their advantage. Sinclair drove towards the byline and provided a low centre which came off the Villa defender Kevin Toner and into the goal. Initially, it appeared that Lee Barnard had made the connection, but replays suggested Toner was the unfortunate man.
Daniel Johnson was a constant thorn in Saints’ side. He twice struck from outside the penalty area, but found Saints’ Northern Irish shotstopper Johns in good form. However, Johnson wasn’t to be denied midway through the first half.
After a mix-up in the Southampton backline, JOHNSON ran through to strike left-footed past Johns for 2-1.
Lee couldn’t connect with a low free kick into the Villa six-yard box, before Stiber had a shot blocked at the other end.
Stiber then engineered space to shoot just over, as Villa piled on the pressure – however it was Saints who were to have the final say.
Harrison Reed whipped in a perfect corner into the six-yard box, and TURNBULL headed home his first goal of the season for 3-1.
FULL TIME: SOUTHAMPTON U21S 3-1 ASTON VILLA U21S
Southampton U21s: Johns, McCarthy, Stephens, Turnbull, Targett, Reed, Flannigan, Lee (Moore), Sinclair, Barnard, Rowe (Seager). Unused substitutes: Britt (GK), Colmer, Mugabi.
Aston Villa U21s: Siegrist, Webb, Donacien, Toner, Kinsella, Cowans, Lyden, Calder, Stiber, Robinson, Johnson. Unused substitutes: Wilden, Watkins, Sellars, O'Brien, Strain.