By james art The Blues took the lead in the first half when Saints defender Meg Collett scored an own goal.
Remy Allen made two changes from the side that thrashed Pompey 5-0 in the south coast derby at Fratton Park last weekend.
Freya Gregory and Paige Peake dropped to the bench, while Allen picked Milly Mott and Rianna Dean from the start.
The Saints got off to a tough start against Birmingham, who started the day top of the Women’s Championship.
Goalkeeper Fran Stenson was called upon to make a double save to deny Tegan McGowan. The England youth international parried the initial effort before pouncing on the loose ball.
The opener did come for the Blues three minutes later when Collett unluckily turned Lucy Quinn’s header into her own net.
The Ireland international, who was born in Southampton, saw her shot from a tight angle deflect off Collett and bounce over the line.
The Saints tried to rally but failed to connect in the final third as the last ball let them down.
Amy Merricks was forced into an early substitution just before half-time – L. Quinn was unable to continue and was replaced by Ellie Mason.
Things got worse for the Saints when the visitors doubled their lead five minutes after play resumed. Rebecca McKenna pulled it back for Ag to sweep from close range.
Allen turned to loanee Gregory, introducing her in place of midfielder Alice Griffith, in an attacking move that would change their fortunes.
But it was Birmingham who looked more likely to score again but Ivana Fuso was denied twice by Stenson.
saints: Stenson, Collett, Mott, Bourne, Purfield, Griffiths (Gregory, 57′), Palmer, Kendall, Rowe, Dean (Thompson, 85′), Pike.
Unused subs: Rednell, Haaland, Brown, Peake, Peplow, Nohasiarsoa.
Birmingham: Thomas, Quinn, Ag, Akpam, McKenna, Herom, Quinn (Mason, 41′), Holloway, Harrison-Murray (Cho, 70′), McGowan, Magill (Fuso, 70′).
Unused subtitles: Szperkowska, Harris, Lawley, Wilson, Worthy, Baker.
Referee: Joan Horwood.
Attendance: 2,117.