This bold saga is set in the year 1660 and begins with John Wilmot, Second Earl of Rochester (Depp), delivering his prologue, the main themes of which are his fondness for drink, his sexual proclivities, and his disdain for his audience.
King Charles II (Malkovich) decides to summon his great friend, the Earl, back to London, retracting a year-long banishment for humiliating him, after only three month's exile. Rochester arrives in London to find his friends in a bawdy house; they are known as the "Merry Gang" and include George Etherege (Hollander) and Charles Sackville (Vegas).
On the street, Rochester comes across a thief, Alcock (Coyle), whose frankness about his dishonesty impresses Rochester. He hires Alcock as his gentleman on the spot. The Merry Gang introduce its newest member, 18-year-old Billy Downs (Friend). Rochester warns Downs, "Young man, you will die of this company."
Rochester invites Downs to attend a play with the Merry Gang, where they see actress Elizabeth Barry (Morton) getting booed off the stage and then refusing to participate in a curtain call. Rochester is taken with Barry, and secures her re-employment with the theatre company after she is initially fired.
Rochester invites Barry to meet him at the playhouse the next day to coach her in acting, and she hesitantly accepts. Barry's acting improves dramatically and she delivers a brilliant performance in her next production. The King then approaches Barry, asking her to spy on Rochester to keep track of his progress. A loyal subject, she agrees.
Charles, in need of money from France, asks Rochester to write a play in honour of the French Ambassador's visit. The King requests it be a "testament" to his reign. Rochester writes Sodom, or the Quintessence of Debauchery, a scathing satire of the King's reign, which he claims is indeed "a testament to Charles" — just what the King had asked for.
The play involves live sex acts, vulgar imagery, and a brutal portrayal of the King, played by Rochester himself. At the premiere, Charles coolly interrupts the play, coming up onto the stage to confront Rochester. Later, Downs is killed in a sword fight outside the home of a Constable; Rochester backs away from his dying friend, whispering, "I told you."
Hiding from the King in the English countryside and sick with symptoms of syphilis, Rochester peddles phony gynaecological "treatments" for women, including the selling of "potions" made from Alcock's urine. Rochester's face has become disfigured by syphillitic gummata, which he hides beneath a mask. Charles eventually tracks down Rochester, but decides that the worst punishment possible is to simply "let you be you."
Rochester returns to his wife, Elizabeth (Pike), admitting to having been constantly under the influence of "the drink" for five years straight. It becomes apparent that despite Rochester's health and infidelities, Elizabeth continues to love him.
Meanwhile, Charles' unpopular choice of heir, his Roman Catholic brother James, Duke of York, has led to a showdown with Parliament, which introduces the Exclusion Bill to deny James the throne. Rochester makes a dramatic entrance into Parliament, wearing a silver nose-piece and heavy pancake makeup to conceal the ravages of syphilis and hobbling on two canes.
He makes a brief but effective speech, rationally and eloquently denouncing the Bill. As Rochester then hobbles off, the subsequent vote kills the proposed Bill. He goes to see Barry, who reveals they had a daughter together, ironically named Elizabeth like his wife. She rejects him.
Rochester returns home to his deathbed, where he dies aged thirty-three with Elizabeth, his mother, a priest summoned to "bring God to him" as she did not want Rochester to die as an atheist, and Alcock.
Before he dies, Rochester asks the priest to recite from Book of Isaiah, chapter 53; he also asks his wife to retell the story of how he had abducted her as an 18 year old lady when they fell in love. The film then cuts between Rochester's actual death, and the death scene of The Man of Mode, the play about him written by his friend Etheridge. In a final irony, Elizabeth Barry is playing his wife on stage.
The film closes as it opens, with an epilogue. Rochester slips into the background in the wavering candlelight, sipping his drink and asking repeatedly, growing less arrogant and more vulnerable with each utterance: "Do you like me now?"