After spending the first 82 minutes of a scrappy and niggly encounter as a virtual spectator, the England under-21 striker popped up in typical fashion to grab a 1-1 draw that hadn't looked likely after Southampton had taken the lead on the stroke of half-time through Premiership top scorer James Beattie.
This certainly wasn't one for the purists - neither side kept possession or passed the ball as well as they would have liked - and the calm influence of Michael Carrick in the Hammers midfield was sorely missed for much of the game.
Having failed a late fitness test on the groin injury he picked up on duty with England under-21s in Portugal last week, Carrick was replaced by Lee Bowyer - returning from a two match suspension - as the only change from the team that beat Sunderland at Upton Park two weeks ago.
That meant Fredi Kanoute stayed on the bench as Defoe and Les Ferdinand continued up front, while Paolo Di Canio missed out altogether after suffering a stomach upset.
In a frenetic and congested start, Southampton attempted to pin Hammers back with a series of long balls towards in-form striker Beattie. It was Beattie who enjoyed the first opening of the game after just five minutes when, with Ferdinand lying injured on the edge of Hammers' penalty area, he fired a fierce low cross into the six-yard box, but Repka was thankfully on hand to clear well.
Hammers settled down after that, though, and came close themselves a few moments later when Joe Cole's corner from the left was met by Glen Johnson, whose header down into the six yard box was cleared.
The young defender was then involved again as Hammers wasted two excellent chances to take the lead in the space of a minute. First he found Bowyer with a clever pass that saw the former Leeds midfielder cut the ball back invitingly for Ferdinand, who screwed his shot wide from just eight yards out.
Johnson then coolly intercepted a Saints attack with a well-timed tackle before the ball found its way out to Ferdinand again, who this time found his accuracy with a magnificent cross that saw Trevor Sinclair dive full length to head just inches wide from the edge of the penalty area.
Bowyer then tested his range with a dipping free-kick from 30 yards that flew just over the bar and, as the halfway mark in the first half passed, Hammers were clearly on top.
As the interval approached, Roeder's men struggled to make the most of the greater possession, with Cole in particular finding it frustratingly difficult to pick the right pass from advanced positions, but it still came as a surprise when Saints took the lead with just two minutes of the half remaining.
A long ball into the box was headed partially clear by Repka, but Marsden picked up the loose ball on the left and clipped it to the far post, where, with Sinclair sleeping, Beattie stole in unmarked to stab the ball past David James from six yards out.
Roeder was forced to make a change at half-time, Edouard Cisse replacing Steve Lomas, and Hammers began to show a bit more urgency in the attacking third of the field. Sinclair came close again when he fired in a snap-shot that Niemi superbly tipped over, while Cole saw a stinging left-foot effort held by the Saints keeper.
Roeder then made a second substitution, as Ferdinand expectedly made way for Fredi Kanoute, but the Frenchman's arrival didn't have any immediate impact and it was Southampton who almost extended their lead as the second half wore on.
Beattie curled in a free-kick that James comfortably held, while Ormerod turned Ian Pearce and cut the ball back into the six-yard box before Sinclair thankfully cleared.
Substitute Kevin Davies then should have done better when he raced into the box but clipped his shot straight at James, and on 70 minutes the hosts wasted a glorious chance to make the game safe, as the unmarked Michael Svensson somehow headed over from just six yards out.
That close shave lifted Hammers, and Kanoute almost levelled with his first real involvement in the game when he cut in from the right but saw his shot blocked by two defenders. The same fate then befell Defoe after Sinclair had lost his bearings while in possession just eight yards from goal, while Kanoute was left kicking himself after miscontrolling when he would have been in the clear.
With just eight minutes remaining, though, Defoe struck. Johnson's long throw from the right cleared most of the Saints defence and the young striker, who hadn't had a sniff all afternoon, popped up six yards out to hook the ball past Niemi and into the net in front of the ecstatic Hammers fans.
With Bolton Wanderers and Leeds United both gaining maximum points from their fixtures against Manchester City and Charlton Athletic respectively, a point at least was compulsory for Hammers today and, once again, the predatory instincts of Jermain Defoe came to the rescue when they were needed most.