Saturday's Championship win for Saints is the first time they have won their opening two league games for 23 years.
Veteran striker David Connolly's close-range header on the half-hour mark was enough to secure victory for Nigel Adkins' men, who survived a late Barnsley rally after substitute Richard Chaplow was sent off on 84 minutes for a rash challenge on Jay McEveley.
The result means Keith Hill's side are yet to score a goal or win a game this season.
Scott Wiseman, Nathan Doyle and David Perkins all returned to the Barnsley starting line-up after being rested for the Carling Cup in midweek.
Goalkeeper Kelvin Davis, skipper Dean Hammond, fellow midfielders Adam Lallana and Jack Cork, and striker David Connolly all returned to Southampton's side having also been rested during the week.
Southampton began the brighter of the two sides. Barnsley struggled to get into any sort of rhythm, much to the home fans frustration as lone striker Craig Davies found himself isolated for the majority of the first-half.
Much of the Saints' good work came through Adam Lallana, who was drifting in from the right-wing to great effect. He should have opened the scoring midway through the first-half, but his delayed shot was well blocked by Jimmy McNulty.
The visitors eventually took the lead on the half-hour mark, the 34-year-old Connolly taking advantage of poor Barnsley defending and hesitant goalkeeping from David Preece to head home from close-range, his second goal of the season.
Connolly almost doubled his side's lead minutes later, but could only drag his effort wide of Preece's post.
The Barnsley players were fortunate to go in at half-time with only a one goal deficit and their supporters voiced their disapproval, causing Tykes boss Allen to shuffle his side at the interval, moving Danny Haynes to partner Davies in attack.
The switch paid almost immediate dividends, but the former Ipswich striker's tame effort was easily saved by Southampton goalkeeper Davis.
The change in tactics failed to make any significant difference to the game however, as Southampton dazzled their opponents with their swift passing and moving. Reuben Noble-Lazarus and Ricardo Vaz Te, introduced for the home side, struggled to see the ball as Southampton became content to retain possession. Indeed, the visitors should have put the game beyond doubt with eight minutes to go, but Lallana's scuffed effort failed to test Preece.
But the game changed with six minutes left when Southampton substitute Chaplow was dismissed, his studs up challenge to McEveley's midriff deservedly earning him a straight red card.
That sparked a late Barnsley flurry, who three times came within inches of snatching an injury-time equaliser. Vaz Te twice forced great saves from Davis, while Miles Addison's effort was somehow cleared off the line with the last kick of the game.