In 1983, ailing millionaire J. Cochran Darrow has discovered the gates and found that they make time travel possible. Darrow organizes a trip to the past for fellow millionaires to attend a lecture by Samuel Taylor Coleridge in 1810. He hires Professor Brendan Doyle to attend and give expert commentary. One of the magicians, Doctor Romany, happens to spy the time travelers and kidnaps Doyle before he can return. Doyle manages to escape torture and flees back to London, now trapped in the 19th century.
Doyle joins a beggars guild and meets a beggar named Jacky. He plans to meet and befriend William Ashbless, a wealthy poet that Doyle has studied profusely, in order to gain a benefactor. Doctor Romany scours the city for Doyle with his legion of murderous beggars, led by the clown-magician Horrabin. At the same time, Doyle discovers that Darrow has remained in the 19th century to search for Dog-Face Joe, a body-swapping werewolf, in hopes of bribing Joe into granting him a healthy new body. Doyle himself becomes targeted by Joe, receiving the poisoned body of Darrow's former bodyguard, but manages to cure himself of the poison before dying.
In his new body, Doyle realizes that he himself is the historical Ashbless. He copies down Ashbless' poetry from memory and deduces his own future from his study of Ashbless' life. Using this knowledge, he continues to thwart the magicians' plans. After Romany discovers a gate to the 17th century, Doyle follows him through and stops his attempt to change the past. Meanwhile Darrow successfully contacts Dog-Face Joe and organizes a deal in which Joe will provide Darrow with healthy bodies and allow him to live forever.
Doyle is kidnapped and brought to Muhammad Ali's Egypt, where the magicians' Master tempts him with resurrecting his dead wife if he will tell them the secrets of the time-gates. Doyle resists and kills the Master. Meanwhile, Jacky discovers Darrow's secret and kills him along with Dog-Face Joe. Doyle returns to London, where the last magician, Romanelli, kidnaps him, Jacky, and Coleridge. In a drugged stupor, Coleridge frees Horrabin's twisted menagerie of monsters, allowing him and Jacky to escape. Romanelli escapes with Doyle to the underworld, but is eaten by Apep while Doyle is rejuvenated on board the sunboat of the god Ra. Doyle meets back up with Jacky and discovers that not only is Jacky secretly a woman, she is his future wife.
Decades later, after living out Ashbless' entire life, Doyle goes out to meet his historic date with death. Doyle discovers that his intended murderer is a duplicate of himself that the Master had made in Egypt. Doyle kills the duplicate, thereby supplying the corpse for his death, and boats away into an unknown future.
As in Powers's later novel, The Stress of Her Regard, The Anubis Gates features a number of the Romantic Poets as characters. In addition to Coleridge, there is Byron (alongside the fictional 19th century poet William Ashbless created by Powers and James Blaylock). Other real people charactrized in the novel are the famous publisher John Murray and the physician who treated Byron for a fever while he traveled in Greece was named Dr. Romanelli.
The novel intertwines a number of real events into the story such as the massacre of the Mamluk beys by Muhammad Ali in 1811 and the failed rebellion by James, Duke of Monmouth against James II in the 1680s.
The ship, Blaylock, that Doyle claims he came to England on is named after friend James P. Blaylock.