Andreas Pereira's superb strike proved in vain as a brace by Ryan Seager, taking his tally to the campaign to eight goals, earned the hosts the three points.
After a quiet opening, the Reds may have been enjoying the larger share of possession but with little threat and the home side broke through on 26 minutes. Some static defending allowed Seager to collect an incisive pass by Jack Flannigan and the confident 16-year-old shuffled inside to scoop a clever finish over Pierluigi Gollini.
Lone striker Sam Byrne at least worked Chris Johns following a pass by Pereira but the Irishman was often isolated in attack and the Saints mustered another attempt when the lively Omar Rowe's shot was well handled by Gollini.
Soon after the restart, Southampton doubled their lead thanks to another cool piece of marksmanship by the promising Seager, who again escaped his markers to round Gollini and make it 2-0.
Byrne and Pereira had shots easily fielded by Johns as United attempted to mount a response and Belgium youth international Pereira supplied a lifeline with 17 minutes remaining. After cutting inside from the left, the creative No10 unleashed a splendid long-range drive that swerved away from Johns to nestle in the corner of the net.
Despite pressing, Paul McGuinness' side were unable to find an equaliser with Seager passing up the best late opportunity at the other end as he blazed over when looking likely to complete his hat-trick. Liam Grimshaw also had to make an important challenge in the dying seconds to thwart the dangerous Seager.