Chris Wood scored a late winner as Birmingham sealed their second successive Europa League victory.
Joseph Akpala's low strike gave Brugge an early lead before David Murphy tapped home Chris Burke's low cross.
Adam Rooney and Nikola Zigic wasted golden chances before Wood fired in Marlon King's cross at the end.
But the game was marred by a head injury to Birmingham's Pablo Ibanez, who was stretchered off with his team-mate Guirane N'daw in tears.
The victory saw Birmingham become the first English side to win at Brugge's Jan Breydelstadion and join Brugge on six points at the top of Group H.
Blues boss Chris Hughton brought in striker Zigic starting for his first game in the Europa League, while Boaz Myhill replaced Colin Doyle in goal after his error in the victory over Maribor.
But the former Hull keeper was beaten inside four minutes when Nabil Dirar's low cross was deftly flicked home by Akpala from eight yards out.
Brugge threatened to run away with the game as they picked holes in Blues' shaky backline, with Ibanez and Stephen Caldwell looking distinctly wobbly at the heart of the defence.
But the visitors fought their way back into the game and created a half chance when Keith Fahey blasted over from a clever corner rolled to the edge of the box.
And they snatched an equaliser in the 27th minute when Murphy sneaked into the box unmarked to finish of Burke's low cross at the back post.
It signalled a complete change as Birmingham took charge and went close to going in ahead at the break.
Murphy went close to a second with a 25-yard curling free-kick that was well saved by Colin Coosemans while Rooney blasted high and wide after racing clear onto a long ball.
Brugge regrouped at half time but could not find a way through a resolute Birmingham defence.
And the Blues wasted a glorious opportunity midway through the half when the lively Burke picked out Zigic on the penalty spot, only for the Serb to head just past the post.
Hughton showed his ambition by bringing on strikers Wood and King off the bench.
But the game was brought to sickening halt late in the game when Akpala clashed heads with Ibanez, who lay motionless on the pitch for 10 minutes before being stretchered off.
It looked like the game was going to peter out to a subdued finish until Wood's stunning late intervention.
King turned smartly on the right wing and his low shot was fired into the roof of the net by the New Zealander from six yards out.