The main character of Sebastian Barry's The Secret Scripture is 100-year-old Roseanne McNulty, who has spent more than half of her life in Roscommon Regional Mental Hospital, a place for the insane. As she nears the end of her life, she decides to write an account of her earlier years and the reasons why she was institutionalized. She keeps the details of her life in a journal hidden under the floor of the small room she has inhabited for more than fifty years.

Dr. Grene, the head of the hospital, is in charge of closing the institution for good. The building is soon to be demolished, and the patients must be assigned to different locations, depending on the state of their mental health. Some of the patients will be sent to other psychiatric wards. Others will be returned to society. Dr. Grene is in the process of evaluating the remaining patients when he comes across Roseanne McNulty. At first he pays her little mind, but when he learns of Roseanne's past, Dr. Grene becomes fascinated by her story.

At first he does not trust her memories. But in the course of Roseanne recalling her life before entering the mental institution, she recounts the history of the political and religious conflicts of Ireland during the 1920s and 1930s. As Dr. Grene researches some of the stories Roseanne tells him, he discovers that a lot of what she says is true. An account recorded by Father Gaunt, a Catholic priest who was a steady and often painful influence on Roseanne's life also corroborates Roseanne's testimony.

Dr. Grene's portion of the narrative comes from notes he keeps on his patients, so much of the story is shared between Roseanne's accounts and Dr. Grene's observations and analysis. In this way, the theme of this story of truth is explored. Is any history truthful or is history tainted by the observer? Can memories be trusted? Or are all historical accounts subjective?

Barry's 2008 novel, The Secret Scripture, won the James Tait Black Memorial Prize, the Costa Award, and was shortlisted for the prestigious Man Booker Prize. The novel has been praised for its lyricism but criticized for its too-pat ending. Sheila Cobb, writing for the Winston-Salem Journal found the book very satisfying on many different levels. Cobb stated that book offered not only a literary writing style but also a sense of compassion and history. The novel contained "excellent characterization and a compelling plot."