Chris Hughton's men had gone in front through defender Curtis Davies' header at Pride Park but were quickly pegged back by Jason Shackell's equaliser.
Nigel Clough's side then capitalised on their momentum as Steve Davies fired them in front before the break and the hosts held on for three points against an unfamiliar Birmingham side who created plenty of chances but are clearly yet to really gel.
Hughton's side are bidding for a quick return to the top flight this season but have been weakened by a player exodus this summer which has seen the likes of Craig Gardner, Sebastian Larsson, Barry Ferguson, Roger Johnson and Ben Foster all leave.
Five of the visitors' starting XI were new faces with former Inverness striker Adam Rooney on his own up front. Derby had plenty of new recruits involved too, among them Frankie Fielding, in goal, as well as Jamie Ward, Shackell, Kevin Kilbane and Craig Bryson.
Derby started well and after Lee Croft came close in the first minute, settled into the game nicely.
Birmingham had a bit more going forward, though, and at the other end Keith Fahey headed wide wastefully from Chris Burke's cross while Jordon Mutch rattled the bar with a header from Jean Beausejour's cross.
The opening goal came in the 19th minute through Davies, as the former Aston Villa centre-half leapt to head home from Mutch's corner.
Seven minutes later the Rams were level, however, as Shackell headed Ben Davies' free-kick past new Blues goalkeeper Boaz Myhill in the 26th minute.
Rooney headed wide in the 28th minute and Beausejour was denied by Fielding as City pressed but it was Derby who snatched the half-time lead.
It came courtesy of striker Steve Davies, who was gifted time on the ball before unleashing a shot which caught out Myhill and left the keeper beaten from 20 yards.
Fahey and Burke had half-chances for Birmingham early in the second half but Derby twice came close to extending their lead through Ward and Steve Davies, the former hitting the bar with a header.
Mutch twice fired wide with speculative efforts for the visitors. Rooney had a header saved and Hughton's side were denied a penalty shout when the striker claimed to have been pushed by Shackell.
Birmingham should have equalised when Burke's excellent foray forward saw him hit the post with a chip but from the rebound, right-back Stephen Carr failed to keep his shot on target.
Ward had another chance for Derby as the lively tempo continued and Birmingham substitute Chris Wood added a physical presence up front, but could not help force an equaliser.