The film starts in London, as a young woman (Emma Stone) jumps from a bridge to her death. She is later recovered by a disfigured scientist named Godwin Baxter (Willem Dafoe) and reanimated as an entirely different person named Bella, who behaves with the mentality of a small child and refers to Godwin as “God”.
During one of Godwin’s lectures, he calls upon Max McCandles (Ramy Youssef) to join him and become his assistant, along with his maid Mrs. Prim (Vicki Pepperdine). Max meets Bella and quickly becomes smitten with her despite her condition. While working together, Godwin tells Max that after he recovered Bella’s body from the water, he saw that she was pregnant, and he replaced her original brain with that of the baby, hence her lack of maturity. Bella views Godwin as something of a father figure.
Max spends time with Bella, trying to help her advance her intelligence. When he starts telling her about places around the world, Bella’s interest in going out increases, something that Godwin tries to forbid her from doing. He is eventually convinced to join Bella and Max for a picnic in a nearby park. A struggle ensues when Bella tries to leave their coach again, and Godwin chloroforms her to calm her down.
When she wakes up, Bella starts to discover self-pleasure and begins trying to masturbate. Godwin later tells Max that he thinks there is a mutual love between Bella and Max, and suggests that he ask for her hand in marriage. Max admits he does have feelings, and he eventually does ask Bella for marriage, on Godwin’s condition that they live with him.
Godwin is visited by a lawyer named Duncan Wedderburn (Mark Ruffalo), who later meets Bella and quickly takes a liking to her. Duncan offers Bella a chance to join him on a trip to Lisbon, even though Godwin would not allow it. She announces her intentions to Godwin and Max, who both express displeasure, but while Godwin lets her go, Bella kisses Max and chloroforms him so he will not try to pursue her further.
Bella and Duncan travel to Lisbon, where Bella enjoys new cultural experiences, as well as constant sex marathons with Duncan, which she calls “furious jumping”. Bella later travels out in the city on her own, viewing things from a fantastical perspective. Duncan invites Bella to join him with other higher class people, though she finds herself taking interests separate from his own. Bella engages in hyperactive dancing during one evening at dinner, which Duncan joins in. He then starts to fight another man who lays eyes on Bella.
Back in London, Max notices Godwin is missing Bella in her absence, but he wants to continue his research without her. He attempts a similar experiment on another woman called Felicity (Margaret Qualley), but her intelligence does not develop as quickly as Bella’s did.
Duncan soon starts to grow exasperated with Bella and his inability to control her. He smuggles her in a large trunk onto a cruise ship as they make their way toward Alexandria. On the ship, Bella meets passengers Harry Astley (Jerrod Carmichael) and Martha Von Kurtzroc (Hannah Schygulla), whose point of views she begins to share when they tell her about philosophy. Duncan becomes more unhinged as Bella’s interests expand beyond his own, and he attempts to attack Martha, which just gets him restrained and whacked in the face with her cane. When they reach Alexandria, Harry shows Bella a group of lower class people in the city, some dead in the streets, which horrifies her to the realities of the world and leads her to have a breakdown before Harry restrains her.
Bella gathers Duncan’s money and gives it to the crew of the ship for what she thinks is a generous donation (they simply pocket the money). With no funds left, Bella and Duncan are removed from the ship in Marseille, but she says goodbye to Harry first. The pair end up in Paris, where Bella comes upon a brothel and seeks employment and housing by Madame Swiney (Kathryn Hunter). Duncan becomes disgusted by Bella fornicating with multiple men, then becomes pissed when he learns she had emergency funds given to her by Godwin. Bella later befriends a fellow prostitute named Toinette (Suzy Bemba), who introduces her to socialism and also engages in sexual activity with her.
Duncan eventually has a breakdown and gets institutionalized. He writes to Godwin, who is falling heavily ill. He sends Max to visit Duncan, who tells him what Bella has been up to. She is brought back to Godwin’s estate in London to see him again. After reuniting with Godwin and coming back to good terms with him, Bella and Max plan to proceed with getting properly married, him not caring about her recent sexual exploits. However, just as the ceremony is going underway, it is interrupted by General Alfie Blessington (Christopher Abbott), who addresses Bella as his wife, Victoria. He says he has come to reclaim her and takes her away back to his home.
Bella learns from Alfie that as Victoria, they would enjoy being cruel to the lower class, and that she claimed her baby was a great trouble to her. Bella realizes that she had committed suicide to get away from her horrible marriage. When she tries to leave, Alfie aims a gun at her and orders her to drink a chloroform-laced cocktail. She throws the drink in his face and causes Alfie to shoot himself in the foot before passing out.
Bella returns to Godwin and lays in bed with him and Max as he dies peacefully. Bella is later shown continuing Godwin’s research along with Max, Mrs. Prim, Felicity, and Toinette. Alfie has his brain swapped out with that of a goat, and Felicity’s intelligence is growing. Bella spends the afternoon reading with a light smile on her face.