Ralph Hasenhuttl's side had broken the deadlock through a controversial Romain Perraud effort, but Declan Rice rescued a point for the visitors, whose four-game winning run was brought to a halt as the Saints avoided a fifth successive defeat.
Despite struggling to get out of their own half in the opening exchanges, it was Southampton who ended up taking the lead at St Mary's, as left-back Perraud's deflected effort nestled into the bottom corner off of Ben Johnson.
There was a real air of controversy about the opener, as referee Peter Bankes got in the way of Jarrod Bowen attempting to intercept the ball to Perraud, but VAR saw nothing wrong with the goal.
A galvanised Hammers side pressed hard for the equaliser before half time, and Southampton were dealt a blow with Armel Bella-Kotchap suffering an apparent shoulder injury, with Duje Caleta-Car coming on in his place.
Southampton's one-goal lead remained intact at the break, but West Ham's persistence paid off in the 64th minute, as Rice received the ball from Said Benrahma on the edge of the area before curling home to level the match.
The energy appeared to have been sapped out of Hasenhuttl's side, as West Ham urgently looked to find a winner at St Mary's, and the hosts made four changes at once to try to claw their way back into the game.
It took 36 minutes until Southampton finally had a shot in the second half, with Ibrahima Diallo missing the target, and the game ended with the spoils shared.
David Moyes's side now occupy 11th place in the table before Liverpool take on Manchester City, and Southampton remain in 18th - now level on points with 17th-placed Wolverhampton Wanderers but behind on goal difference.
A trip across the South Coast to Bournemouth now awaits Southampton on Wednesday night, while West Ham will take on Liverpool at Anfield in their midweek contest.