Tonda Eckert brought Flynn Downes, Kuryu Matsuki, and Shea Charles back into the team as expected. Jack Stephens and Cyle Larin replaced Nathan Wood and Ross Stewart, respectively, as the Saints' head coach freshened things up after beating Arsenal on Saturday.
Southampton started brightly and were 2-0 up within twenty minutes. First, Kuryu Matsuki turned in from close range in a central position, and then Flynn Downes kept a drive low from the edge of the box to make it two.
Wrexham got themselves back into the game in the 34th minute when a clear foul by Kieffer Moore on Harwood-Bellis was ignored by the referee, allowing Josh Windass the opportunity to finish coolly.
Cyle Larin restored Southampton's two-goal lead on the hour when the Canadian latched onto a misplaced pass on the halfway line before running through and slamming the ball into the far corner.
Substitute Ross Stewart turned in from close range to make it 4-1 from a Welington cross before Finn Azaz got a well-deserved goal to make it five!
Player ratings: formation (4-2-3-1)
Goalkeeper and defenders
Goalkeeper - Daniel Peretz: 6/10 Southampton’s best goalkeeper in years has helped transform the club's fortunes. Wrong-footed for Wrexham's goal.
Right back - James Bree: 7/10 The English full back has been brilliant since returning from his loan at Charlton, and suits the profile Tonda Eckert needs on the right-hand side. Bree's low free-kick into the near post rebounded out for Flynn Downes to volley home. His crossing caused problems for Wrexham.
Centre back - Taylor Harwood-Bellis: 7/10 Clearly fouled for Wrexham's first goal when Kieffer Moore ran into his back, allowing Josh Windass to go on and score. Not one of his finest performances, but Harwood-Bellis still made six big clearances on the night.
Centre-back - Jack Stephens: 6/10 Stephens was a bit sloppy for Wrexham's goal, diving in on Windass instead of holding the Wrexham striker up. Struggled to deal with Kieffer Moore and Josh Windass. Looked classy on the ball, and his calmness steadied the ship at key times.
Left-back - Ryan Manning: 6/10 A solid performance from the Saints left-back, but he tired after an hour and was replaced by Welington.
Midfielders
Centre midfield - Flynn Downes: 7/10 Downes returned to action in terrific style after missing the FA Cup win against Arsenal due to suspension. His controlled strike from a rebounded set-piece in the 22nd minute doubled Southampton's lead. Was largely anonymous for long spells as Wrexham bypassed midfield with long balls.
Centre midfield - Shea Charles: 9/10 The Northern Ireland international was full of energy in the first half and caused Wrexham problems with his forward running and his range of passing. Head and shoulders, the best player on the pitch. His interceptions and blocks were vital when Wrexham pressed.
Attackers
Attacking midfield (left) - Sam Edozie: 6/10 Edozie was a constant threat down the left, and his low ball across the six-yard box should really have been turned in by someone. Max Cleworth might have been grateful to see Léo Scienza on the bench, but when he brought Edozie down in the 20th minute, it led to Saints' second goal. Struggled with his final ball and was withdrawn for Léo Scienza on the hour.
Attacking midfield (centre) - Finn Azaz: 9/10 The Republic of Ireland international was unlucky not to open the scoring himself, when he headed against the crossbar from close range in the tenth minute. His next involvement was to provide an exquisite assist for Kuryu Matsuki. Struck the post with a good effort from the edge of the area in the 75th minute. Scored in the final ten minutes to make it 5-1.
Attacking midfield (right) - Kuryu Matsuki: 7/10 The Japanese winger opened the scoring in the 12th minute with a low shot inside the near post after a smart pass from Finn Azaz. Good energy all match.
Striker - Cyle Larin: 8/10 Headed against the bar in the tenth minute, which almost worked out as an assist, but Finn Azaz could only manage to do likewise and head against the bar from four yards out. The Canadian should have scored five minutes before half-time when he blazed over a bouncing ball when clean through. Held the ball up well all game and latched on to a misplaced pass in the second-half to score Southampton's third. Withdrawn shortly after.
Substitutes
Léo Scienza 7/10
Ross Stewart: 7/10
Welington: 6/10
Nathan Wood: N/A
Cameron Archer: N/A