In 1920s Copenhagen, landscape artist Einar Wegener lives a blissful life with his wife, Gerda, a portrait painter. During a portrait session, Gerda asks Einar to pose as a female model for one of her paintings. This seemingly innocuous request sparks an intense revelation for Einar, awakening a deep-seated identification with the female gender. Einar begins to adopt the persona of Lili Elbe, initially as a secretive exploration but gradually making more public appearances, straining the couple's relationship and challenging societal norms. Gerda, although initially supportive and inspired by this muse for her own art, struggles with the emotional and social implications of her husband's transformation.

As Einar's journey progresses, Lili becomes more prominent, and the psychological and physical toll intensifies. They both seek guidance from various medical professionals, ultimately leading them to pioneering German doctor Kurt Warnekros. Gerda remains by Lili's side, grappling with her own identity and emotions in the process. The narrative unfolds through their trials and triumphs, exploring themes of identity, love, and understanding. The story renders a poignant portrait of personal and mutual transformation amidst the backdrop of a less accepting era.