The infant Joan of Ingleheim is born in the year 814 to a Saxon woman named Gudrun and her English husband, the Canon of Ingleheim. The village midwife Hrotrud delivers baby Joan after a dangerous, complicated labor. The cold and hateful canon is severely disappointed to have a daughter, believing that, in addition to being worthless, women are the source of sin.

Pope Joan is the story of a medieval-era young woman who is intellectually brilliant and motivated in her desire to learn all she can about religion and medicine. Over time Joan, disguised as John Anglicus, is eventually afforded opportunities at levels of power that most men never reach. Her secret, the fact that she is a woman, is known to only one man, the knight, Gerold. This gifted woman's only opportunities to contribute to her changing world are dependent upon her façade of manhood.

Tutored as a child by the forward thinking Greek, Aesculapius, Joan finds an opportunity to attend the palace school in Dorstadt with her brother, John. When she survives a brutal attack by Norseman on the day of her dreaded arranged wedding, fifteen year old Joan escapes in her dead brother's hooded cape, and joins the monastery of Fulda using the name of John Anglicus. She lives and studies as a monk at the abbey, and learns to practice medicine under the abbey's resident physician.

Joan travels to Rome, still in disguise as a man, and proceeds to prove herself a remarkable healer and the voice of reason among men whose restrictive religious beliefs cripple them to common sense. After a momentous series of events, Joan is elected Pope of Rome, and serves fairly and honorably in that capacity until her death. Her story is virtually written out of history due to the bizarre discovery of her sexuality, and the fact that she is able to accomplish so much under the noses of the powerful men of that time. Although Joan lives as a man, the one love in her life is for Count Gerold, whom she encounters many times over the course of her life. When Gerold is killed, Pope John Anglicus, or Joan, miscarries a child and dies, leaving Rome with an embarrassing and disgraceful piece of history to deal with.

Only as John Anglicus, is Joan able to live the remarkable life of a scholar, physician, Catholic priest and finally, Pope, during a time when are considered valuable only for child-bearing.