Nikola Zigic scored the only goal of the game when he headed in Sebastian Larsson's free-kick on 65 minutes.
West Ham's Demba Ba came off the bench and also almost marked his debut with a goal but his shot hit the post.
Birmingham had their defence to thank for a clean sheet, although they were lucky to escape when Manuel da Costa shot off-target and then headed wide.
The hosts went close on several occasions with Victor Obinna and Robbie Keane impressive in the first half, yet they had trouble carving out many clear openings and the defeat leaves them at the bottom of the Premier League on goal difference, two points from safety.
It is a huge blow for the Hammers after encouraging displays in their last two games where they beat Blackpool and Nottingham Forest in the FA Cup.
Birmingham were also victorious the last time these two teams met, thrillingly overturning a deficit in the second leg of the Carling Cup last month.
But with both sides in the Premier League's bottom three before the game began, the three points at stake made for a cagey match.
The Nigerian forward lined up on the left of a front three with Keane in the middle and Frederic Piquionne on the right, and it was from Keane's lay-off that the former Portsmouth striker curled a shot straight at Ben Foster on 20 minutes.
The Irishman's ability to hold the ball up and find space in congested central areas was a help to Avram Grant's side, and his lay-off allowed Obinna to shoot left-footed but he was off-target.
For Birmingham, David Bentley attacked with purpose on a couple of occasions and shot over early on, but Alex McLeish's midfield were struggling to link up with the front pair of Zigic and Cameron Jerome.
Roger Johnson came closest to scoring for the visitors in the first half when he headed over from six yards following Lee Bowyer's cross, but he made up for that by producing some sterling defending to head clear Obinna's bullet centre.
Grant had to make a last-minute change to his starting line-up with Matthew Upson replacing the injured James Tomkins in the heart of the defence but Upson, himself, could only last until half-time.
Da Costa replaced the England defender and it wasn't long before he was under pressure when Bentley found Zigic but the Serbian's header was wide.
McLeish then made what looked like a negative decision to take off Jerome and replace him with midfielder Larsson just before the hour.
But the Swede justified the faith his manager showed in him when his set-piece from the left was headed in at the back post by Zigic - his sixth goal of the season.
West Ham argued that the free-kick awarded to Birmingham was a soft one, with Mark Noble barging over Bentley, but the appeal emphasised the growing frustrations of the West Ham supporters.
Carlton Cole replaced the increasingly ineffective Piquionne with Keane switching to the right, but the introduction of Senegalese forward Ba almost had an instant impact when he hit the post following a free-kick.
Urged on by an expectant crowd, West Ham were pressing for the equaliser, but struggled to produce any further saves from Foster.
And as Birmingham retreated, it was left to defender Da Costa to help out in attack.
He had a long-range shot which left Foster scrambling across goal, and then his far-post header was narrowly wide.
Zigic then almost doubled his tally near the end after good hold-up play, but shot straight at Robert Green and, even though he was not involved for long periods of the game, his telling contribution proved decisive.
West Ham left the field to boos at the end and they will now need to reinvigorate themselves to exit the drop zone once again.
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