Sadio Mané's late goal earned Saints a deserved point from their trip to Liverpool to preserve the side's unbeaten away record.
Ronald Koeman’s men had looked set for late heartbreak when substitute Christian Benteke headed home with 77 minutes gone.
But Mané nipped in to convert from close range four minutes from time to ensure his team did not go home empty-handed.
The Senegalese forward was sent off in stoppage time for two bookable offences, but Saints held on to pick up a point for their efforts.
Koeman’s options had been boosted by the return of Maarten Stekelenburg, who went straight into the starting XI after missing last weekend’s draw with Leicester due to a back problem.
Also starting was fellow Dutchman Jordy Clasie, who made his full Premier League debut following a substitute appearance in that draw with the Foxes.
Liverpool, meanwhile, had two ex-Saints in the starting XI for new manager Jürgen Klopp’s first league game at Anfield in the form of Nathaniel Clyne and Adam Lallana.
And it was the hosts who started the game brighter, with Cédric having to make an important block to deny Philippe Coutinho before the resultant corner was flicked wide of the near post by Emre Can.
Lallana, who scored 60 times in his 265 appearances for Southampton, then tested Stekelenburg with a low shot that the goalkeeper duly swallowed.
Saints soon found their rhythm, though. Dušan Tadić’s 12th-minute corner was headed over the bar and into the Kop by José Fonte, before some smart work by Serbian played in Graziano Pellè only for the forward’s drive to be blocked by Martin Škrtel.
Simon Mignolet found himself in a spot of bother moments later as he struggled to deal with a backpass under pressure from Mané, before Ryan Bertrand’s cross skimmed off the head of Mamadou Sakho to fall nicely for Steven Davis – but his tame effort was gathered by the Reds goalkeeper.
Liverpool responded, with Coutinho looking their main source of danger – the Brazilian cut in from the left and shot twice in quick succession, with one effort flying just over the bar and the other being absorbed by Saints captain Fonte.
Liverpool captain James Milner fizzed a shot just wide of Stekelenburg’s left-hand post on the half-hour, before seeing another drive blocked by Victor Wanyama after being teed up by Lallana.
Saints’ best chance of the first half arrived six minutes before the break when Davis’s clipped free kick picked out the run of Virgil van Dijk, but the Dutchman’s downward header was superbly clawed away from goal by Mignolet after bouncing off the Anfield turf.
Van Dijk was causing trouble once again moments later, heading Tadić’s cross over Mignolet only for it to be nodded away from danger by midfielder Lucas.
Alberto Moreno then blazed over the crossbar after being played through by Lallana as a frenetic opening period drew to a close with Saints having enjoyed more of the first half’s chances.
Having only tested Stekelenburg once before the break, Liverpool made a half-time change, replacing one Belgian striker in the ineffective Divock Origi with another in the form of Benteke.
The hosts started the second period well, mounting sustained pressure on the Saints defence – although the struggled to find shooting opportunities until Moreno flashed an effort across the target five minutes before the hour mark.
Saints quickly responded to that chance, with Cédric manoeuvring his way down the right before dinking a teasing ball into the box that was just an inch too high for Pellè.
Mané then threatened to get away from Moreno down the left, but the Spaniard did well to track the Saints man before producing an inch-perfect sliding tackle to rid him of the ball in the box.
With the game entering its final third, Koeman made his first substitution, replacing Tadić with the more defensive James Ward-Prowse, while Klopp threw on Roberto Firmino for ex-Saint Lallana.
Saints then introduced Juanmi in place of Clasie, but it was one of the Reds’ substitutes who broke the deadlock soon afterwards. Milner was afforded too much time in crossing from the right, and his curling delivery was powered home by the head of Benteke.
Koeman responded by bringing on Gastón Ramírez for his first league appearance for Saints in 14 months, and he had a big hand in the side’s equaliser. Ward-Prowse’s free-kick was nodded on first by Fonte and then looped towards goal off the head of the Uruguayan, with Mané stealing in at the back post to force the ball home.
As Saints defended doggedly late on, Mané was shown two yellow cards in quick succession to mean Koeman's side ended the game with ten men. But they kept the hosts at bay superbly to ensure the unbeaten away record in the Premier League was maintained.
Liverpool (4-3-2-1): Simon Mignolet; Nathaniel Clyne, Martin Škrtel, Mamadou Sakho, Alberto Moreno; James Milner, Lucas, Emre Can; Adam Lallana (Roberto Firmino 67), Philippe Coutinho (Jordan Ibe 83); Divock Origi (Christian Benteke 46). Unused substitutes: Adam Bogdan (GK), Kolo Toure, Joe Allen, Connor Randall.
Goal: Benteke (77)
Booking: Milner (85)
Southampton (4-2-3-1): Maarten Stekelenburg; Cédric, José Fonte, Virgil van Dijk, Ryan Bertrand; Victor Wanyama, Jordy Clasie (Juanmi 75); Sadio Mané, Steven Davis (Gastón Ramírez 80), Dušan Tadić (James Ward-Prowse 64); Graziano Pellè. Unused substitutes: Kelvin Davis (GK), Maya Yoshida, Oriol Romeu, Steven Caulker.
Goal: Mané (86)
Booking: Mané (90+1)
Sent Off: Mané (90+3)
Referee: Andre Marriner