A Kenwyne Jones double strike and a Rudi Skacel goal were enough to give Southampton a 3-0 half-time advantage. Birmingham hit back in the second half with strikes by substitute Cameron Jerome and Nicklas Bendtner.
Substitute Bradley Wright-Phillips thought he had killed the game off for the Saints when he scored with his first touch after coming on after 77 minutes only for Birmingham to grab a late consolation when Radhi Jaidi headed home.
The goal sparked pushing and shoving between Southampton goalkeeper Kelvin Davis and defender Chris Baird. The result killed hopes of Birmingham topping the table and Southampton moved up to seventh spot in the Championship race.
Southampton got their first goal in the 14th minute when Jones picked up a loose ball near to the area and turned and fired a shot passed a despairing Maik Taylor and into the top left-hand corner of the net.
Striker Jones doubled his side's advantage three minutes later when he met a Jermaine Wright cross with a towering header that flew into the back of the net.
Jones then turned provider for Southampton's third goal when he headed a ball back to Skacel. The midfielder picked up the ball and drilled home a left-footed drive into the bottom left-hand corner of the net.
Birmingham come out after the break with renewed vigour and striker Bendtner hit a speculative shot from 15 yards that just cleared the Southampton crossbar.
Jones should have got his hat-trick in the 55th minute when he headed goalwards but, as the ball looped up, he somehow got in the way of his own header as it hit him on top of the head on the goal-line.
Jerome came on for Neil Danns and made a huge impact for his side as, in the 68th minute, Sebastian Larsson put over a teasing corner that he lashed into the net.
The Southampton defence were panicking and Bendtner put his side back in the game with a shot from 20 yards that beat Davis in the Southampton goal.
Southampton substitute Wright-Phillips scored with his first touch before Jaidi ensured a nervous last few minutes by heading home his side's third, but it was too little too late.