After getting their noses in front, Posh squandered further chances but held out in the face of a spirited Saints fightback after the break.
The visitors had crashed 4-1 at home to Crystal Palace in their opening game of the Championship season on Saturday, leaving them bottom of the first league table of the season.
Southampton's towering Bartosz Bialkowski had to be alert to tip over from Aaron McLean in the first minute, but even the goalkeeper's height was no help when he was beaten by Grzegorz Rasiak's own goal after 21 minutes when an inswinging corner from Dean Keates caused all sorts of problems for the Saints defence.
Keates was also involved when Posh doubled their lead five minutes later, the former Walsall man's shot coming off Bialkowski's legs before George Boyd was quickest to react, stabbing a shot into the empty net.
It should have been three on 36 minutes when McLean blazed over after being set-up by Chris Whelpdale.
Southampton rode their luck and struck swiftly with Nathan Dyer beating two defenders before Rasiak went some way to redeeming his earlier blunder sticking out a boot to convert at the far post in the 37th minute.
Posh quickly recovered their composure and McLean squandered another great chance when beating Saints' offside trap only for Bialkowski to advance and make the most of his exceptional reach to snatch the ball down.
Saints upped the tempo after the break and home goalkeeper Shwan Jalal denied Rudi Skacel for the second time on the night with a full-length save and the Baghdad-born keeper was just as impressive dropping on an effort from Bradley Wright-Phillips at the far post.
Posh held their nerve through five minutes of added time to complete a great day for chairman Darragh MacAnthony, who finally completed his purchase of the club.
The Irish property developer paid just £1 to former owner Barry Fry, but is also repaying Fry's investment over the last five years, thought to be over £1million.
Peterborough 2 Southampton 1
