Sam Allardyce's West Ham played most of the top-of-the-table encounter with 10 men, but maintained their one-point advantage at the summit with the draw.
In a chaotic few minutes, Matt Taylor was sent off following a clash with Billy Sharp, which came after the hosts were awarded a penalty at Upton Park.
Captain Mark Noble stepped up and converted the 21st-minute spot-kick, but Southampton equalised in the second half when Dutchman Jos Hooiveld scored in the 75th minute.
Meanwhile, Cardiff City moved to within three points of second-placed Southampton with a 3-1 win at home over Peterborough United.
Midfielder Peter Whittingham scored directly from a corner, Rudy Gestede netted a header and teenager Haris Vuckic, on loan from Newcastle United, was also on the scoresheet as the Welsh side took a three-goal lead into the break.
Striker Paul Taylor struck a stoppage-time consolation for the visitors as promotion contenders Cardiff ended a three-game winless run.
Coventry City moved off the bottom as Gary McSheffrey's two penalties led them to a surprise 2-1 win over Leeds United.
Birmingham City extended their unbeaten league run to 10 matches after a lacklustre 0-0 draw at home to Hull City, while Gary Taylor-Fletcher's brace helped Blackpool move into fourth courtesy of a 3-1 win at lowly Doncaster Rovers.
Strugglers Bristol City salvaged a point as Brett Pitman's late double saw them secure a 2-2 draw against Crystal Palace, while Noel Hunt hit the winner in Reading's 1-0 victory at Derby County.
Middlesbrough held on with 10 men to secure their first league win of 2012 with a 2-1 victory at home against Nottingham Forest, while Craig Forsyth's 80th-minute goal saw Watford to a 3-2 win against Leicester City.
Elsewhere, Brighton and Hove Albion remain unbeaten this year after a 2-2 draw at home to Millwall, Michael Chopra scored the winner in Ipswich Town's 1-0 win at Portsmouth and Burnley overcame Barnsley 2-0.
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