The only goal of the game came from Dan Burn - on loan at Yeovil last season and their hero in May's Wembley League One play-off final - who scrambled home from a corner early in the second half.
The Glovers were dealt a blow inside six minutes when goalkeeper Marek Stech was forced off with an injured hand, to be replaced by goalkeeping coach Gareth Stewart.
However, it was Yeovil with the first shot on target, Paddy Madden stinging Darren Randolph's gloves from distance.
Randolph was again called into action on 20 minutes parrying defender Byron Webster's arrowed volley before reacting immediately to Madden's header.
The Blues did not test the stand-in keeper until the half hour mark when Andrew Shinnie's attempt was well stopped.
Gary Johnson's men enjoyed the best of the first half, not allowing the visitors any rest in possession, with the Midlands club reduced to half-chances and two bookings for cynical challenges.
Birmingham were sent out early after the break with the words of manager Lee Clark ringing in their ears, and it had its desired effect in the opening moments of the second half. Shane Ferguson's corner was met by Burn, now on-loan at the Blues from Fulham but whose Wembley goal in May sent Yeovil into the Championship.
Birmingham then kept the ball well to quieten the home crowd, and Burn sent a second effort curling wide.
The Glovers talisman last year was League One top goalscorer Madden, and in front of the watching Ireland coach Marco Tardelli, it was the Dubliner who had the first glimpse of an equaliser, nodding a Sam Foley cross comfortably into the hands of Randolph.
The opportunity sparked the Somerset men into action and Webster's thundered header drew some athleticism from the City stopper, tipping the chance onto the crossbar.
Like at Millwall in the previous week, last term's top-scorer was withdrawn for Michael Ngoo, and the Liverpool loanee was immediately in the action, forcing a foul from Burn. From the resulting free-kick, Sam Hoskins failed to take advantage.
Johnson's men were typically dogged and organised but they could not prevent Shinnie wriggling his way in behind and bringing a save out of Stewart.
Yeovil won their first-ever Championship game at the New Den last week with a goal in the 88th minute, and the green and whites almost drew level from the same man - Ed Upson curling his free-kick just wide of the far post - but Birmingham held strong to take all three points.