It had looked like an early goal from the diminutive Emanuele Giaccherini would see Paolo Di Canio's men take three points back to the north east.
Standing at just 5ft 5in, the smallest player of the pitch headed home a Sebastian Larsson corner unmarked in just the third minute.
Poor finishing, fine goalkeeping from Kieren Westwood and plain old bad luck looked set to deny Saints, only for centre-back Jose Fonte to head home two minutes from time.
It was just reward for Mauricio Pochettino's side, who came into the clash buoyed by a fine opening-day win at West Brom and another big-money acquisition.
Following moves for Dejan Lovren and Victor Wanyama, Dani Osvaldo arrived this week from Roma for a fee that could reach £14.5million.
The forward was named amongst the substitutes at St Mary's, where another Italy international struck the first blow.
Larsson sent across a corner from the left found Giaccherini unmarked and he nodded home to the delight of the hardy 1,867 travelling fans.
It was hardly the start Southampton wanted but one they responded well to.
Rickie Lambert slipped through a fine ball to Jay Rodriguez, who slotted past Westwood and wheeled away in celebration - only for the linesman to rule the sixth-minute leveller out for offside.
Saints again came close 10 minutes later, with Westwood this time the man in the way.
James Ward-Prowse, one of three 18-year-old academy graduates in the starting line-up, sent over a looped cross to Lambert, with only an exquisite Westwood save down to his right preventing the England international heading home.
Neither side was managing to dominate play but Sunderland were looking the more confident, epitomised by a cheeky in-swinging Larsson corner that almost caught Artur Boruc off guard.
A Rodriguez snap-shot deflected wide off Craig Gardner when play returned to the other end, with Jozy Altidore proving a handful for Southampton's defence.
Lambert powered a header over at the back post, while Altidore, Fonte and Adam Lallana all had penalty appeals waved away before half-time.
Nathaniel Clyne and record-signing Osvaldo were introduced for the second period, with the latter close to having an immediate impact.
The Italian's deft pass saw Lallana with a clear shot on goal, only for Modibo Diakite to swoop in with a fantastic, late tackle.
The Saints captain saw a right-footed half volley curl just wide shortly afterwards, before an Osvaldo cross found Rodriguez, only for the Saints attacker to head straight at Westwood from close range.
Westwood did well to tip a long-range Lambert strike around the post but Saints were still struggling at the back, with only the onrushing Boruc preventing Altidore doubling the Black Cats' advantage.
It was Southampton in the ascendancy, though, and they kept knocking on the visitors' door.
Lambert and Rodriguez were the next to threaten, although the intensity began to peter out with 15 minutes remaining.
Osvaldo headed into the ground under pressure from John O'Shea as the match entered the closing stages as tempers began to fray.
Ironic cheers met referee Lee Mason's award for a foul on the new boy late on - a decision that led to Saints equalising at the death.
Ward-Prowse floated in the free-kick and centre-back Fonte met the ball with a powerful header that at last beat Westwood.
Rodriguez saw a shot deflect wide as Saints pushed for another in stoppage time, but there were to be no further goals.