In 1926, British wizard and “magizoologist” Newton “Newt” Scamander arrives in New York City. He encounters Mary Lou Barebone, the non-magical (“No-Maj” or “Muggle”) head of the New Salem Philanthropic Society, who preaches that witches and wizards are real and dangerous. Attempting to recapture a Niffler that escaped from his suitcase of magical creatures, Newt meets No-Maj Jacob Kowalski, an aspiring baker, and they unwittingly swap suitcases. Porpentina “Tina” Goldstein, a demoted Auror of the Magical Congress of the United States (MACUSA), arrests Newt for breaking magical law. Since the suitcase in his possession only contains Jacob’s baked goods, Newt is released, much to Tina’s embarrassment. At home, Jacob opens Newt’s suitcase, inadvertently freeing several creatures into the city.
After Tina and Newt find Jacob and the suitcase, Tina takes them to her apartment and introduces them to Queenie, her Legilimens sister. Jacob and Queenie are mutually attracted, though American wizards are forbidden to have any contact with No-Majs. Newt takes Jacob inside his suitcase, magically expanded to house various creatures including an Obscurus, a parasite that develops inside magically gifted children when their abilities are suppressed; Newt extracted it from a young girl who died, as those afflicted rarely live past the age of ten.
After they recapture two of the three escaped beasts, Tina returns the suitcase to MACUSA, but they are arrested, as officials believe one of Newt’s creatures is responsible for killing Senator Henry Shaw Jr., who was actually attacked by an Obscurus. The Director of Magical Security, Percival Graves, accuses Newt of conspiring with the infamous dark wizard Gellert Grindelwald, and decides to destroy Newt’s suitcase and obliviate Jacob’s recent memories. Newt and Tina are sentenced to death, but escape aided by Queenie and Jacob, who retrieve Newt’s suitcase. A tip from Tina’s goblin informant Gnarlack leads the four to recapture the last of the escaped creatures.