Kazeem Olaigbe's wonder strike was not enough as United fought back late to take all three points at Snows Stadium.
Saints’ side got younger once more this week with defender Will Tizzard and midfielder Seamas Keogh coming in as Allan Tchaptchet and Caleb Watts dropped out.
Amongst the substitutes were midfielders Kami Doyle and Kaya Tshaka, both making their first B team squad of the season.
Despite the hosts enjoying the majority of the early possession it was United who forced the first saves of the game.
Keeper Jack Bycroft, who had an inspired performance to help Saints on their way to three points against Derby last-time-out, making two saves low down to first his left and then his right just shy of the ten-minute mark.
Then Saints had a chance of their own; Sam Bellis picking up the ball in midfield and playing through Jayden Smith, whose effort was saved at point-blank range by United’s Matej Kovar.
The hosts enjoyed a spell of neat passing play in and around the United box on 14 minutes, Ethan Burnett, Lucas Defise and Sam Bellis all combining well with the visitors penned in.
Burnett continued to impress with his range of passing as he then found Smith with a disguised, looping through ball.
With the twenty-minute mark coming and going United struggled to build on the two quick fire chances they had ten minutes prior.
Perhaps sensing this, and fresh off of his match-winning goal last-time-out, Kazeem Olaigbe ran at the United defence, skipping past three men before a heavy touch allowed Kovar to collect.
United appeared to kick into gear around the half hour mark, Bycroft called into action again to tip Mark Helm’s cross-goal shot around the post.
A stroke of fortune on 36 minutes almost gave the visitors the opening goal.
Bycroft was disposed by Joe Hugill, whose first effort with cleared off the line by the backtracking Tizzard before his second clipped the far post.
It was a sign that United were certainly growing into the game and another opportunity for Saints to respond.
But United continued to flow forward; Hugil who had been at the heart of everything good for the visitors seemingly one-on-one with Bycroft on 41 minutes before a vital James Morris block.
Eventually the half came to a close with both sides enjoying a share of the possession and chances.
United were the first to have an effort as the second half got underway, Snows Stadium continuing to be baked in sunshine.
In the 56th minute came Lewis Payne’s first appearance for the B team set up this season, another youngster gaining his first experience of the first-team’s playbook in competitive action.
Just shy of the hour mark came another superb Bycroft save as the Saints keeper tipped Alvaro Fernandez’ free-kick over the bar.
Saints’ first chance of the game was created by Zuriel Otseh-Taiwo down the left flank, finding a deep cross to Smith who headed just over.
Smith then was involved again, grabbing possession off of Helm and put through on goal with a tight angle and forcing Kovar into another one-on-one save.
Another youngster made his B team debut on 70 minutes, 15-year-old Kami Doyle coming on to replace Tizzard who appeared to pull his hamstring.
With the second half turning into a fairly even affair compared to the first, it would take a moment of magic for the deadlock to be broken.
Olaigbe picked the ball up just outside the United penalty area, before firing a superb effort into the top left corner to give Saints the lead.
It’s Olaigbe’s third in four games since the turn of the new year, with the youngster clearly enjoying life as a B team regular.
As expected United came back in search for an equaliser almost instantly, forcing Bycroft into two more top saves.
Their response came on 83 minutes, McCann played through by Will Fish and firing across goal to level the scores.
Two minutes later the game was turned on its head, McCann cutting in from the opposite flank this time to put United ahead for the first time this afternoon.
Saints looked to equalise but United stood strong, meaning it’s a first defeat in three for Saints at Snows Stadium.
Next up is another Totton-based fixture, as Arsenal visit in Premier League 2.