The home side took an early advantage when David Henen did well to beat the last man before steering the ball past Will Britt in the Southampton goal.
Jonjoe Kenny and Brendan Galloway added Everton’s second and third before half time, before Courtney Duffus had one ruled out for offside.
Southampton were unable to recover, but they did pull a goal back through Bevis Mugabi 20 minutes from time as Bolton Wanderers boss Neil Lennon watched on from the stand.
The game had an incident-packed opening foray, as the visitors had a half-chance scrambled away after the ball found itself at the feet of Southampton’s top goalscorer Ryan Seager, following a bad clearance from Russell Griffiths.
But it would be the lone glimmer of hope in a dour first half for the south coast outfit, and Everton started it off by pulling ahead inside 180 seconds.
Henen staked his claim for a call up to the senior squad in the victory, and showed fantastic pace to race past Jason McCarthy after nipping in to dispossess Mugabi, before coolly finishing inside the left-hand post.
And it didn’t take the Belgian-born winger long to involve himself in another goal, this time turning back an over-hit corner for captain Kenny to head the game’s second.
The Toffees continued to press forward and should have had two more goals courtesy of Duffus, but his first effort was cleared off the line thanks to a combined effort from McCarthy and Britt, and his second just whistled past the post.
Southampton’s struggles continued, and their only other real opportunity in the opening 45 came when Seager went through on goal, but centre back Galloway did well with a last-ditch challenge to take the ball away from the striker.
But just when things were starting to look up for the Saints, Galloway got involved at the other end and turned in Ryan Ledson’s floated cross in off the post to put the game beyond any realistic doubt.
Duffus thought he had finally got his goal on the stroke of half time, but his headed effort was promptly ruled out for offside.
The sides remerged for the second half unchanged, and Southampton looked to get back into game as Seager had a half-volley saved by Griffiths.
Duffus, whose efforts in attack on the evening deserved a goal, had another shot well-saved by Britt, who did well to get down low to his right.
It took 70 minutes, but Southampton finally came into the game as a sustained period of pressure led to Mugabi’s goal, for which the defender prodded home from a corner to make amends for his earlier mistake.
The win sees Everton rise to third in the Barclays U21 Premier League table, closing the gap on Southampton, who remain second, to just two points.
Everton: Griffiths (GK), Jones, Connolly, Ledson, Kenny, Galloway, Williams (Dyson, 84’), Junior, Duffus (Charsley, 75’), Dowell (Walsh, 66’), Henen Subs: Hewelt (GK), Walsh, Langton, Charsley, Dyson
Scorer(s): Henen (3’), Kenny (13’), Galloway (26’)
Southampton: Britt (GK), Flannigan, Wood, Gape, Mugabi, McCarthy (Mason, 60’), Sims, Hesketh, Gallagher, Seager, Sinclair Subs: Mason, Isted, Olomola, Willard, Little
Scorer(s): Mugabi (70’)
Referee: Gary Mellor (Yorks)