Years before the Second Wizarding War, the wizard Gellert Grindelwald goes missing after murdering several aurors (hunters of dark wizards) in Europe. In 1926, the British wizard and “magizoologist” Newt Scamander arrives by ship to New York, en route to Arizona. He encounters Mary Lou Barebone, a non-magical woman (“No-Maj” or “Muggle”) who heads the New Salem Philanthropic Society, which claims that witches and wizards are real and dangerous. As Newt listens to her speak, a Niffler escapes from his magically expanded suitcase, which houses multiple magical creatures. As he attempts to capture it, he meets No-Maj cannery worker, First World War veteran and aspiring baker Jacob Kowalski, and they accidentally swap suitcases. The demoted auror Tina Goldstein arrests Newt for being an unregistered wizard and takes him to the Magical Congress of the United States of America (MACUSA) headquarters. She hopes to regain her former position by showing that he is in possession of magical creatures, which are prohibited in the United States. However, as Jacob’s suitcase contains only baked goods, Newt is released. At Jacob’s tenement apartment, several creatures escape from Newt’s suitcase.
After Tina and Newt find Jacob and the suitcase, Tina takes them to her apartment and introduces them to Queenie, her Legilimens younger sister. Queenie and Jacob are mutually attracted, though American witches and wizards are forbidden to marry or even socially interact with No-Majs. Newt takes Jacob inside his magically expanded suitcase, where Jacob encounters a contained Obscurus, a dark, destructive parasite that develops inside magically gifted children if they suppress their magical abilities. Newt extracted it from a young girl who has died, those afflicted rarely living past the age of ten. Newt persuades Jacob to help search for the missing creatures. As they make their way to the Central Park Zoo, they capture the missing Niffler and avoid arrest by the police. They also find the missing Erumpet in the zoo, who Newt puts back in the case. After re-capturing two of the three escaped beasts, they re-enter the suitcase, which Tina takes to MACUSA. Officials arrest them, believing one of Newt’s beasts is responsible for killing Senator Henry Shaw Jr. They decide to destroy Newt’s suitcase and erase Jacob’s recent memories. Director of Magical Security Percival Graves accuses Newt of conspiring with the infamous dark wizard Gellert Grindelwald. Newt and Tina are sentenced to immediate death, while Queenie figures out what happened. After escaping with the help of Newt’s Swooping Evil and Bowtruckle, which can pick locks, they escape and run into Jacob and Queenie. They escape MACUSA and continue looking for the final escaped beast. Thanks to the help of Goblin gangster Gnarlack, Tina’s old informant, the foursome then find and re-capture the last of the creatures.
Meanwhile, Graves approaches Credence Barebone, Mary Lou’s adopted son, and offers to free him from his abusive mother and teach him magic. In exchange, he wants Credence to find an Obscurus. Graves believes it has caused the mysterious destructive incidents around the city. Credence finds a wand under his adopted-sister, Modesty’s, bed. Mary Lou assumes it is Credence’s wand, but Modesty claims it is hers. When she is about to be punished, the Obscurus is unleashed, killing everyone except Modesty and Credence. Graves arrives and dismisses Credence as being a Squib (a non-magical person of wizard ancestry), and refuses to teach him magic. Credence reveals he is the Obscurus’ host, having lived longer than any other host due to the intensity of his magic. In a rage, he unleashes the Obscurus upon the city.