An early strike from Omar Rowe was built on by a devastating close-range hit from Ryan Seager in the first half to ultimately seal the three points in London.
The Hammers gave Martin Hunter’s side cause for concern in the latter period of the second half when substitute Adrian Wojcik Kosela powered a shot off the crossbar while other attempts were either wayward or prevented.
Wojcik Kosela managed a consolation for his side in the 91st minute though when his dragged effort snuck into the far corner.
Saints employed an approach full of attacking intent from kick-off but it was West Ham who threatened first out of the two sides.
Sebastian Lletget pulled the ball back for striker Elliot Lee to hook a shot towards the far corner, only to see it side-footed away calmly by Josh Debayo.
The early stages saw Southampton be more clinical inside the box as Rowe fired his side into an eighth-minute lead.
Jake Flannigan rolled the ball into space for the winger to charge onto and confidently drill across ‘keeper Raphael Spiegel and into the bottom corner.
Matthias Fanimo troubled the visitors’ defence on two occasions shortly after when his free-kick caused a goalmouth scramble that forced a hacked clearance before a solo effort from the winger saw him evade several challenges and hit a rising, 25-yard drive that flew into the stands.
Lee came even closer for the home side soon after the half-hour mark when a West Ham corner eventually reached the frontman for a volleyed effort that Niall Mason headed off the line.
Any frustration suffered by the hosts at their failure to level the scoring was compounded in the 35th minute when Seager struck a second for Southampton.
Rowe was the provider on this occasion as his corner ricocheted to the feet of Seager, allowing the forward to blast the ball into the roof of the net.
The restart didn’t bring the same energetic start as the first half as Saints did well to nullify any West Ham threat while creating the occasional opening for themselves.
Skipper Jason McCarthy elected not to shoot from an acute angle when a corner found him at the back post and instead pulled back for Seager. The striker’s attempted volley deflected back towards McCarthy but the defender’s goal-bound header was held by Spiegel.
Two minutes later West Ham introduced Wojcik Kosela – replacing the influential Fanimo – who would go on to make an impact of his own twice in the space of four minutes but to no avail.
The first of which saw him rattle the crossbar from a pull-back before he volleyed inches over the woodwork from Lletget’s pass.
Lletget had a go of his own with seven minutes remaining when he made powerful contact on a header from a corner but saw Cody Cropper palm it away.
The hosts eventually snatched a consolation when Lletget and Wojcik Kosela combined to better effect as the latter side-footed into the far corner.
West Ham U21s: Raphael Spiegel, Sam Westley, Lewis Page, Josh Cullen, Emmanuel Onariase, Reece Oxford, Blair Turgott (Kieran Sadlier 37), Elliot Lee, Sebastian Lletget, Matthias Fanimo (Adrian Wojcik Kosela 64). Unused substitutes: Tim Brown, Kyle Knoyle, Amos Nasha.
Goal: Wojcik Kosela (90+1)
Southampton U21s: Cody Cropper, Niall Mason, Jason McCarthy, Will Wood, Josh Debayo, Jake Flannigan, Jake Hesketh, Ryan Seager, Josh Sims, Omar Rowe (Dan Demkiv 85), Sam McQueen. Unused substitutes: Chris Johns, Kyle Clinton, Armani Little, Chris Regis.
Goals: Rowe (8), Seager (35)