Birmingham lost their unbeaten record in the Premiership in an Old Trafford encounter where they were forced to play for two thirds of the game with only ten men.
The Blues had goalkeeper Maik Taylor sent off by referee Mike Dean for a 33rd minute foul on Manchester United's Paul Scholes.
Scholes was up-ended in the box as he tried to round Taylor after running on a delightful weighted pass from Ruud van Nistelrooy.
As Taylor was the last line of defence, Mr Dean was left with no option but to order off the Northern Ireland international and award United the penalty.
Van Nistelrooy, who had missed three of his last four penalties, stepped up to fire the spot-kick low and right-footed into the left corner of the net sending Ian Bennett the wrong way.
Bennett had come on seconds earlier for winger Stan Lazaridis following Taylor's dismissal.
The goal put United on the road to three points, but this was far from a sparkling performance from the Reds.
After a sterile first half, Birmingham should have been level in a spirited opening to the second half.
Within a minute of the restart, Mikael Forssell's header found Jamie Clapham free on the left side of the United box, but he fired his shot straight at keeper Tim Howard, who saved brilliantly at point-blank range.
Three minutes later, Howard again saved well, this time from Stephen Clemence's fierce 25-yard drive.
But the Birmingham revival soon petered out and United increased their lead in the 56th minute.
Phil Neville found Scholes 25 yards from goal and his instant control saw him crash a left-foot shot beyond Bennett and into the net on the bounce.
Bennett saved bravely from van Nistelrooy before United made it 3-0 with nine minutes left.
Mikael Silvestre found the marauding Ryan Giggs midway inside the Birmingham half and he exchanged passes with substitute Diego Forlan before placing his left-foot shot beyond Bennett and into the net from just inside the box.