Girl Genius presents an alternate history "where the Industrial Revolution has escalated into an all-out war"[13] due to the battles between "Sparks" – highly charismatic mad scientists with supernormal abilities in one or more sciences. The setting is "Europa," which is geographically similar if not identical to Europe.
The protagonist, Agatha Heterodyne, at first seems to be nothing more than a struggling student at Transylvania Polygnostic University. When Baron Klaus Wulfenbach and his son come to investigate irregularities at the university, a seemingly coincidental sequence of events leads to a surprising revelation: Agatha discovers that she is one of the last living members of the Heterodyne family, a line of powerful (and often murderously insane) Sparks.