Joe Ledley and Cameron Jerome netted the City goals, but when Dexter Blackstock pulled one back for the Saints midway through the first half, it made for an uncomfortable time for the home defence.
The Bluebirds had Michael Ricketts back up front while Paul Parry displaced Kevin Cooper in midfield. Rhys Weston failed a late fitness test so Neal Ardley continued at right-back
George Burley's side showed six changes to that beaten by Sheffield United on their last outing.
A flick on by Ricketts in the third minute gave Jerome a sight on goal but Matthew Mills deflected for the first corner of the game.
Three minutes later City went ahead with a well worked goal from Ledley.
Ricketts sent Jason Koumas down the right and he slid the ball into Jerome. The 19-year-old striker crossed to the far post where Parry pulled it back and Ledley had the easy task of side-footing into the net.
Jerome doubled the score in the ninth minute when he raced on to a superb through ball from Ledley to shoot past Antti Niemi in the Saints goal.
The visitors were back in the game in the 25th minute when Glenn Loovens failed to clear a long punt down the middle and Blackstock toe-poked into the net.
Ten minutes before the break Jerome broke through once again but Niemi came out quickly to block.
Neither side made changes during the interval but both managers would have asked their defences to tighten up for the second period.
Brett Ormerod replaced Kenwyne Jones in the 71st minute as Burley went looking for at least a point and Saints quickly won a corner that Chris Barker had to head clear under pressure.
City countered with Alan Lee replacing Ricketts and there were anxious moments in the home defence as first Ormerod and then Theo Walcott went close to an equaliser but the Bluebirds hung on for a deserved victory.