Cradle and All is a medical thriller. It revolves around three major characters. Anne Fitzgerald is retired nun turned private investigator. She is hired to investigate a series of unlikely events, including two virgin pregnancies. Kathleen is the first of two pregnant virgins. Kathleen lives in Newport, Rhode Island with her family. Thus, much of the story takes place in Newport. Kathleen denies that she has had sex, yet is unable to remember fully the night she conceived. Therefore, her pregnancy is surrounded by speculation, and even her parents are not supportive. Colleen is the second of the virgin girls. Colleen lives in Maam Cross, Ireland, with her ill mother. She attends a Catholic school for girls. She, too, denies having had sex, but finds herself pregnant. The Irish community is not supportive of her and ridicules her publicly, forcing Colleen to be schooled from home in seclusion. Both girls are independently examined by doctors who confirm that they are indeed pregnant virgins. The mystery of their conceptions is reminiscent of the Immaculate Conception and piques the curiosity of the Catholic Church, both in America and at its headquarters in Italy.

Additional supporting characters also attempt to understand the mysterious pregnancies. Father Nicholas Rosetti is sent by the Pope to research the girls and their situation. Just before his death, Pope Pius XIII entrusted Father Rosetti with all of the details of the prophecy. Father Rosetti has this additional information to utilize when investigating the girls. Father Justin O'Carroll is sent by the Cardinal to investigate as well. Anne, Father Rosetti, and Justin each face the forces of good and evil during their quest. They will hear demonic voices, feel temptation to act in unspeakable ways, and some will experience physical pain. As the story unfolds, the reader also discovers that simultaneous world-wide catastrophies are occurring. Droughts, famine, floods, viruses, genocide, and polio outbreaks are harming humans in large numbers. The Blessed Mother foretold the birth of a savior and also the birth of Satan's son. This prophecy, combined with the world-wide disasters, leads church authorities to conclude that one of the virgins will deliver a savior who will end the suffering. The converse is that the other virgin will birth a powerful beast.

During their research, Anne and Justin rekindle a loving relationship that had previously been suppressed. Father Rosetti is the most deeply disturbed of the three—the Devil visits him frequently. The trio cross the world trying to unravel the mystery. Old medical records provide the details that help Father Rosetti to determine that Colleen is carrying Satan's child. The birth process creates a surge in Kathleen's memory, and she realizes that although she is a virgin, her child's conception is not divine. The true child of God is born unto Anne in the epilogue.