From Hell takes as its premise Stephen Knight's theory that the murders were part of a conspiracy to conceal the birth of an illegitimate royal baby fathered by Prince Albert Victor, Duke of Clarence, slightly modified: the involvement of Walter Sickert is reduced, and Knight's allegation that the child's mother was a Catholic has been dropped.

In an appendix added to the collected From Hell, Moore writes that he did not accept Knight's theory at face value (and he echoed the then-growing consensus that such claims were likely hoaxes), but considered it an interesting starting point for his own fictional examination of the Ripper murders, their era and impact.