Einar and Greta Wegener are a married couple. They are both painters who met while Greta was studying under Einar at the Royal Academy in Denmark. While Einar is relatively successful with his landscape paintings, Greta is still struggling for her own work to gain some recognition. When she is commissioned to paint the portrait of Anna Fonsmark, a famous opera singer, Greta asks her husband to pose for her when her subject isn’t available. She asks him to hold a bouquet of lilies wile wearing Anna’s dress, and seeing how he seems so pleased with the experience, she suggests they call his alter-ego “Lili”.
One day, they venture out to the Artist’s Ball with Einar dressed as Lili, and tell the others in attendance that she is a cousin of Einar. At the ball, Lili meets and flirts with a man named Henrik. They kiss, but Lili gets a bloody nose, prompting Greta to believe Henrik has hurt Lili. This event is the start of a slew of of outings with Lili. Greta’s portraits of Lili gain some praise from a Parisian art critic, while Lili herself becomes the subject of attention of the painter Henrik. However, not wanting to admit she is a man, Lili ends her relationship with him.
The couple moves to Paris, where Greta tracks down Hans, a childhood friend of Einar who has now become an art dealer. Greta gains much popularity in France, but her husband stops painting all together.He begins visiting a peep show in order to learn how to move more like a woman. Einar becomes increasingly melancholy with being Einar. He feels as though he should be Lili all the time, and contemplates suicide. Greta and her brother Carlisle take to see many doctors, who all misdiagnose him and want to either commit him for schizophrenia, or perform a lobotomy. It isn’t until they meet Professor Bolk, that they discover that the best option is for Lili to live her life to the fullest. The professor has developed a surgery to physically change a man into a woman.
When Einar goes meets Bolk in Dresden, he visits the area before checking himself in the clinic. He finds himself on a terrace overlooking the Elbe river, and he then decides on Lili’s last name: Elbe. She would now be known as Lili Elbe. When the surgery in performed, it is discovered that Einar had been born with ovaries which were undeveloped, making him also biologically female. After the surgery, Lili returns to Copenhagen with Greta. They continue to live together even after divorcing.
Lili and Henrik reunite and he eventually proposes to her. They decide to move to America. Still, Lili confides in Greta about wanting children of her own, and lets her know she will be going back to Dresden in order to have an ovarian transplant surgery. Greta believes this to be too risky and refuses to accompany her. Carlisle is the one who ends up going with Lili to Dresden. The surgery is performed but isn’t without serious complications. Lili is infected, and it is suggested she will not live much longer. Carlisle decides to take Lili out for what the reader assumes is a last walk along the Elbe.