In 1888, Mary Kelly (Heather Graham) and her small group of London prostitutes trudge through unrelenting daily misery. When their friend Ann Crook (Joanna Page) is kidnapped, they are drawn into a conspiracy with links higher up than they could possibly imagine. The kidnapping is soon followed by the gruesome murder of another woman, Martha Tabram (Samantha Spiro); and it becomes apparent that they are being hunted down, one by one as various prostitutes are murdered and mutilated post-mortem.
The murder of Martha and her companions grabs the attention of Whitechapel Police Inspector Frederick Abberline (Johnny Depp), a brilliant, yet troubled, man whose police work is often aided by his psychic "visions." His colleague, Sergeant Peter Godley (Robbie Coltrane), tries to grasp his friend's wild theories. Abberline's investigations reveal that the murders, while gruesome, imply that an educated person is responsible due to the precise and almost surgical method used. Ann is found a few days later in a workhouse having been lobotomized after officials and doctors supposedly found her to be insane, though it is implied this was done to silence her.
Abberline consults Sir William Gull (Ian Holm), a physician to the Royal Family, drawing on his experience and knowledge of medicine. During this meeting, it is revealed Abberline is struggling with opium addiction. Gull's findings, coupled with his superiors impeding his investigations, point Abberline to a darker and more organized conspiracy than he originally thought. Abberline becomes deeply involved with the case, which takes on personal meaning to him when he and Mary begin to fall in love.
Abberline deduces that Freemason influence is definitely present in these crimes. His superior, a high ranking Freemason himself, then makes direct intervention and suspends Abberline. It is then revealed that Gull is the killer. He has been killing the witnesses to painter Albert Sickert (Mark Dexter)'s forbidden Catholic marriage to Crook, who bore his legitimate daughter, Alice. Sickert is actually Prince Albert, grandson of reigning Queen Victoria (Liz Moscrop), and therefore Alice is heiress to the British throne. Gull tells Abberline that "mankind will remember him 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 have Abberline eliminated without leaving any witnesses, but Abberline fights back and kills two of the assassins by overturning a carriage. Gull himself is a Freemason and his increasingly sinister behavior lends an insight into his murderous, but calculated, mind. Rather than publicly charge Gull, the Freemasons decide to lobotomize him to protect themselves and the Royal Family from the scandal. Gull defiantly states he has no equal among men, remaining unrepentant up to his lobotomy, resulting in him becoming invalid just as Ann had been.
Abberline tries to save Mary, but arrives too late, and blames his superior for not helping him or Godley on the cases. Abberline does nothing but watch Mary's mutilated body being taken away. Abberline receives a mysterious letter, which he soon realizes is from Mary, but he decides not to look for her as a way to offer her protection, as the Freemasons may be watching his every move. Abberline decides to burn the letter, knowing that he can never have a normal life.
Mary Kelly was not killed; Gull mistook Ada, whom Liz said was from France (but is from Brussels in Belgium), for Mary and he killed her instead. Mary lives with Alice as her daughter in a cottage on a cliff by the sea. Abberline is found dead of an opium overdose, knowing he can never see Mary again without endangering her. Sergeant Godley comes to pay his respects for the Inspector.Johnny Depp as Inspector Frederick Abberline, sympathetic police officer who investigates the 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 or "bangtail", who builds up a relationship with Abberline and eventually falls in love with him.
Ian Holm as Sir William Gull, a gentleman, retired surgeon and physician ordinary to Queen Victoria, now teaching at the Royal London Hospital.
Robbie Coltrane as Sergeant Peter Godley, the humorous and literary-minded subordinate assistant and friend of Abberline, based on Sgt. George Godley.
Ian Richardson as Sir Charles Warren, a stiff bureaucrat and Abberline's superior.
Jason Flemyng as Netley, the coachman and stooge of the murderer.
Samantha Spiro as Martha Tabram, the first Ripper victim.
Annabelle Apsion as Polly Nichols, the second victim.
Katrin Cartlidge as Annie Chapman, aka Dark Annie, prostitute and gullible third victim.
Susan Lynch as Liz Stride, a spirited prostitute and the fourth victim.
Lesley Sharp as Kate Eddowes, a "mothering" prostitute and fifth victim.
Estelle Skornik as Ada, an old friend of Liz Stride from Brussels and the sixth victim.
Paul Rhys as Dr. Ferral, an ambitious young doctor and specialist in the treatment of dementia.
Vincent Franklin as George Lusk - chairman of a local "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.
The part of Sir William Gull was originally going to be played by Nigel Hawthorne, but when his cancer prevented him from working on the film he was replaced by Ian Holm. The disparity in height between Hawthorne and the much shorter Holm led to some of the scenes being changed.
The film received mixed reviews from critics. Ebert and Roeper gave the film a "two-thumbs up". It currently holds a 57% on Rotten Tomatoes, based on 148 reviews, Critic Consensus: Visually impressive, but this latest Ripper tale is dull and far from scary. E! Online stated it is "two hours of gory murders, non-sequitur scenes, and an undeveloped romance" and gave the film a C-. The New York Post called it a "gripping and stylish thriller". Leonard Maltin gave the film three stars, calling it "colorful and entertaining; an impressive showing for the Hughes Brothers”. Empire's Kim Newman gave the film four out of five stars, praising the "range of squirmingly superior British acting talent" although noting that "the script can't quite sell its Jack as at once a purposeful assassin and a mad killer." Philip French was impressed by the film, praising Depp's "very good" performance alongside those of the actresses who played the Ripper's victims. French also praised the production design and cinematography which evoked representations of London by the artists Whistler and John Atkinson Grimshaw.
The original comic's writer, Alan Moore, criticized the replacement of his "gruff" version of Frederick Abberline with an "absinthe-swilling dandy".
The film grossed $31,602,566 in the United States and $74,558,115 worldwide.