In 1888, Mary Kelly and a small group of London prostitutes trudge through unrelenting daily misery. Their friend Ann Crook is a former prostitute now married to a wealthy painter named Albert, and she has recently given birth to a daughter, Alice. When Ann is kidnapped, the women are drawn into a conspiracy with links to high society. Ann's kidnapping is followed by the gruesome murder of another one of the women, and it soon becomes apparent that each of the prostitutes is being hunted, murdered and mutilated post-mortem by a killer called Jack the Ripper.
The prostitute murders grab the attention of Whitechapel police inspector Frederick Abberline, a brilliant yet troubled man whose police work is often aided by his psychic "visions." Abberline is still grieving the death of his wife during childbirth two years earlier. His colleague Sergeant Peter Godley tries to grasp Abberline's strange theories. Abberline's investigations reveal that an educated person, likely knowledgeable in human anatomy, is responsible for the murders because of the highly precise, surgical methods used.
Ann is soon located in a workhouse after being lobotomized because doctors deemed her violent and insane. It is implied that the operation was performed in order to silence her.
Abberline consults Sir William Gull, a physician to the royal family, drawing on his experience and knowledge of medicine. During this meeting, Gull deduces that Abberline is struggling with opium addiction. Gull's findings point Abberline to a darker, more organized conspiracy than he had originally suspected. Abberline becomes deeply involved with the case, which takes on personal meaning when he falls in love with Mary.
Abberline deduces that Freemason influence is involved in the murders. His superior, a high ranking Freemason, opposes Abberline's methods and suspends him from the case. Thereafter, Abberline persists and discovers that Gull is the killer. Gull was instructed to dispose of all witnesses to the forbidden marriage of painter Albert Sickert to Ann Crook, the mother of his legitimate daughter, Alice. Sickert is revealed to be Prince Albert, grandson of reigning Queen Victoria. Albert is dying of syphilis, which makes baby Alice the soon-to-be heiress to the British throne. Gull boasts to Abberline that he will be remembered in history for giving "birth to the 20th century." Abberline draws his gun, vowing that Gull will never see the 20th century, but before he is able to shoot Gull, he is knocked out by Ben Kidney, another Freemason.
The Freemasons try to eliminate Abberline without leaving any witnesses, but Abberline fights back and kills two of the assassins by overturning a carriage. Abberline rushes to save Mary but arrives too late, and blames his superior for not helping him or Godley on the cases. Gull's increasingly sinister behavior lends an insight into his murderous, but calculating, mind. Rather than publicly charge Gull, the Freemasons lobotomize him to protect themselves and the royal family from the scandal. Gull defiantly states he has no equal among men, remaining unrepentant until the operation, which renders him an invalid like Ann.
Abberline goes to the Ten Bells Tavern in Whitechapel and receives a mysterious letter from Mary. It is revealed that Gull had mistaken another prostitute, Ada, for Mary and killed her instead. To protect Mary, Abberline decides not to look for her, as the Freemasons are still watching him closely. He burns Mary's letter, knowing that he can never have a normal life with her. Sergeant Godley later finds Abberline dead of an opium overdose. Distraught, Godley places two coins over Abberline's eyes and mournfully says, "Good night, sweet prince."
Years later, Mary is shown to have adopted Alice, and the two are living in a cottage on a cliff by the sea.
Johnny Depp as Inspector Frederick Abberline, a sympathetic police officer who investigates the Ripper murders. The consumption of drugs makes him dream scenes from the murders, but he nevertheless conducts the investigation in a rational way.
Heather Graham as Mary Kelly, a young prostitute, who builds up a relationship with Abberline and eventually falls in love with him.
Ian Holm as Sir William Gull, a retired surgeon and physician ordinary to Queen Victoria, teaching at the Royal London Hospital.
Robbie Coltrane as Sergeant George Godley, the humorous and literary-minded subordinate assistant and friend of Abberline.
Ian Richardson as Sir Charles Warren, a stiff bureaucrat and Abberline's superior.
Jason Flemyng as John Netley, the coachman and stooge of the Ripper.
Samantha Spiro as Martha Tabram, prostitute.
Annabelle Apsion as Polly Nichols, prostitute.
Katrin Cartlidge as Annie Chapman, prostitute.
Susan Lynch as Liz Stride, prostitute.
Lesley Sharp as Kate Eddowes, prostitute.
Estelle Skornik as Ada, an old friend of Liz Stride from Brussels.
Paul Rhys as Dr. Ferral, an ambitious young doctor and specialist in the treatment of dementia.
Vincent Franklin as George Lusk - chairman of the Whitechapel Vigilance Committee.
Ian McNeice as coroner Robert Drudge
David Schofield as McQueen
Sophia Myles as Victoria Abberline, Frederick Abberline's late wife.
Joanna Page as Ann Crook, Mary Kelly's friend, who was kidnapped.
Mark Dexter as Prince Albert Victor aka Albert Sickert.
Anthony Parker as Joseph Merrick, The Elephant Man.
loosely based on the graphic novel of the same name by Alan Moore and Eddie Campbell about the Jack the Ripper murders