In 1926, Newt Scamander arrives at the Magical Congress of the United States of America with a magically expanded briefcase, which houses a number of dangerous creatures and their habitats. When the creatures escape from the briefcase, it sends the American wizarding authorities after Newt, and threatens to strain even further the state of magical and non-magical relations.

In 1600, nobleman Orlando inherits his parents’ house, thanks to Queen Elizabeth I, who commands the young man to never change. After a disastrous affair with Russian princess Sasha, Orlando looks for solace in the arts before being appointed ambassador to Constantinople in 1700, where war is raging. One morning, Orlando is shocked to wake up as a woman and returns home, struggling as a female to retain her property as the centuries roll by.