In March 1964, Dr. David Henry finds himself in an emotionally charged situation as he helps deliver his wife Norah Henry's twins with the assistance of nurse Caroline Gill. Their firstborn, a boy named Paul, arrives healthy and perfect, but when the second baby, a girl named Phoebe, enters the world, David quickly realizes that she has Down syndrome. Haunted by the memory of his younger sister June, who passed away at a tender age of twelve due to similar health issues, David grapples with the prospect of heartbreak and decides to place Phoebe in an institution.
Tasked with taking Phoebe to the institution, Caroline is struck by the unacceptable conditions she encounters and, feeling a profound sense of compassion, chooses to raise Phoebe as her own. One day, while running errands, Caroline finds herself stranded in the snow with the baby after her car runs out of gas. Fortunately, she is rescued by truck driver Al Simpson, who drives them back to her home. Meanwhile, David chooses to tell Norah that their daughter has died during birth. Upon learning that Caroline has defied his wishes and is caring for Phoebe, he advises her to act according to her conscience. Hoping for a fresh start, Caroline relocates to Pittsburgh with Phoebe.
The emotional fallout from their daughter's supposed death creates an indelible rift in David and Norah's marriage. Despite moving to a new house, they struggle to reconnect romantically. In Pittsburgh, Caroline begins working as a private nurse for Dorothy "Doro" March's father, Leo, where she embraces her new life, declaring Phoebe to be her child and spinning a partially fabricated tale about fleeing her daughter's father.
As time progresses, Caroline maintains contact with David, sending letters and photographs of Phoebe. David sends financial support but remains distant, fixated instead on his aspirations as a photographer, where he keeps the images of Phoebe and her letters hidden away. Meanwhile, Al often visits Caroline, and a romantic relationship begins to blossom between them.
Fast forward six years, David's obsession with his work intensifies while his relationship with Norah deteriorates further. Norah finds solace in alcohol and becomes overly protective of Paul. In contrast, Phoebe thrives under Caroline's nurturing care, defying David’s bleak predictions of her potential limitations.
With constant support from the community, represented by the Upside Down Society, Caroline advocates for the integration of children with Down syndrome into public schools, offering Phoebe a better life. Al's commitment deepens when he proposes to Caroline multiple times, but she hesitates due to her concerns over his capability as a father. After an incident where Phoebe has an allergic reaction, Al's dedication proves to Caroline that he is truly invested in both her and Phoebe's well-being, prompting her to accept his proposal.
As the years pass, Paul and Phoebe grow into young adults, while Caroline and Al celebrate five years of marriage. David, still burdened by the lies he told, reaches out to Caroline with a request to meet Phoebe and have her connect with Paul. Caroline, however, worries that David might inadvertently hurt Phoebe and chooses to sever communication with him.
As Paul delves into his passion for music, aspiring to join Juilliard, David and Norah's lives remain disconnected, with David pushing for a practical career for Paul driven by a desire for financial security. During a vacation in Aruba, Norah becomes involved in an affair with Howard, leaving David feeling as though he is at fault for their structural issues, further pushing him into solitude and his photographs.
Years later, at age 25, Paul travels and studies music in France, while Phoebe harbors dreams of marrying her boyfriend Robert, who also has Down syndrome, yearning for independence, which prompts Caroline to reflect on her protective instincts. In the wake of a heart attack, David ponders confessing his past to Norah but is unable to confront the truth. Upon his death, Norah discovers his collection of photographs, finally gaining insights into her late husband's internal struggles.
In a poignant visit, Caroline reaches out to Norah, revealing that Phoebe never truly died and is living a vibrant life with her. This revelation leads Norah and Paul to Pittsburgh, where they meet Phoebe for the first time. As Paul drives Phoebe to their father's grave, he envisions the life his twin sister might have led had she not been born with Down syndrome, contemplating the complexity of their family history.
