Carlo Ancelotti’s side were way off the pace on the south coast as first half goals from James-Ward Prowse and Che Adams secured a deserved three points for the Saints.
Everton did look bright in the opening stages with James Rodriguez testing Alex McCarthy and Gylfi Sigurdsson firing against the bar.
But their sluggishness in midfield proved to be Everton’s undoing as Ward-Prowse edged Southampton in front.
The Toffees were caught sleeping from a thrown in into the box and Ward-Prowse raced onto Danny Ings’ pass to fire past Pickford on 28 minutes.
But despite being caught out by Southampton’s opener, Everton fell into their trap once again five minutes.
Ings forced in a cross from the right and with Michael Keane unable to clear his lines, Adams reacted to the loose ball to make it 2-0.
Southampton looked to pick up the initiative again after the break with Pickford called into action to deny Adams and Jannik Vestegaard.
And the visitors afternoon went from bad to worse in the closing stages as full back Lucas Digne was shown a straight red card for a lunge at Kyle Walker-Peters.
Full Time at the St. Mary’s Stadium it’s Southampton 2 Everton 0