The visitors completed the season double over the hosts thanks to goals in either half from Lloyd Dyer and Lucas Akins at St Andrew's.
The result sees them leap-frog over Birmingham, who are now just three points above the drop zone following their latest body blow.
The Italian joined with the St Andrew's club in seventh place just a point off the playoffs, but a disastrous run including 14 defeats now has them just two off the drop zone.
Akins' goal prompted an immediate chant of "we want Zola out" from the disgruntled home fans as Birmingham slipped further into trouble near the foot of the Championship.
And Zola acquiesced resigning within an hour of the final whistle with the club revealing the news in a short statement on Twitter before admitting he regretted not being able to turn things around.
"I'm sorry because I came here with huge expectations and the results, unfortunately, haven't been good. I take full responsibility for that," he said in his post-match press conference.
"I'm the first one to be disappointed by results. If I feel like I cannot help the team, it's better that I leave somebody else to do that."