In the late 1920’s, the actress Anna Larssen of the Royal Danish Theater, having just premiered the role of Orpheus in a new play, could not appear for the last sitting of her portrait, the centerpiece of a new exhibition. Anna makes an unusual suggestion; that the artist, Gerda Wegener, ask Lili Elbe, (at that time known as Gerda’s husband, the artist Einar Wegener), to dress up and pose as Anna. At this sitting Lili is brought to a profound self-discovery, never before acknowledged. Like Orpheus compelled to look back at Eurydice, Lili can never again turn away from the truth of who she is. Despite the support of Gerda, their friends Eric and Hélène, and Lili’s brother Marius, Lili encounters hostility and rejection from her sister Dagmar and later her own mother. Through the efforts of Hélène she is introduced to Professor Warnekros who agrees to operate on her at the Municipal Women’s Clinic in Dresden.

After her first surgery, a dramatic encounter with the King of Denmark leads to an extraordinary decree — Lili is legally recognized as a woman, and her marriage to Gerda is annulled.

Despite the seeming loss of their deep relationship, both Lili and Gerda find temporary love in different quarters, Lili with the perfumer Claude Lejeune, and Gerda with the Italian Major Fernando Porta.

When Claude Lejeune asks Lili to marry him, Lili delays until she can have surgery to become a mother, which Professor Warnekros says he can make possible. He and the Matron of the clinic choose a young woman to be the experimental uterus donor. Neither Lili nor the Young Woman suspect what is in this plan.

Lili, dying from complications of her surgery, writes and thanks the absent Gerda for the flowers she has sent every day from Rome. In return, Gerda sends a final letter. From two distant cities, their voices rise together in a last duet — declaring their love for each other that only grows and never looks back.