In 1926, British wizard and "magizoologist" Newt Scamander arrives in 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. As Newt listens to her speaking about witches and wizards being real and dangerous, a Niffler escapes from Newt's magically expanded suitcase, which houses various magical creatures. As Newt attempts to capture the Niffler, he meets No-Maj cannery worker and aspiring baker Jacob Kowalski, and they unwittingly swap suitcases. Demoted Auror (hunter of dark wizards) Tina Goldstein arrests Newt for the chaos caused by the Niffler and takes him to the Magical Congress of the United States of America (MACUSA) headquarters, hoping to regain her former position. 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 sister. Jacob and Queenie are mutually attracted, though American wizards are forbidden to have any contact with No-Majs. Newt takes Jacob inside his magically expanded suitcase, where Jacob encounters a contained Obscurus, a parasite that develops inside magically gifted children if they suppress their magical abilities. Newt extracted it from a young girl who died, those afflicted rarely living past the age of ten. Newt persuades Jacob to help search for the missing creatures. After they re-capture two of the three escaped beasts, Tina returns the suitcase to MACUSA. Officials arrest them, believing one of Newt's beasts to be responsible for killing Senator Henry Shaw, Jr. 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 erase Jacob's recent memories of magic. Newt and Tina are sentenced to immediate death in secret, but Queenie and Jacob rescue them, and they escape after retrieving Newt's suitcase. Following a tip from Tina's old goblin informant Gnarlack, the foursome find and re-capture the last of the escaped creatures.
Meanwhile, Graves approaches Mary Lou's adopted son Credence and offers to free him from his abusive mother. In exchange, Graves wants Credence to find an Obscurus, which he believes 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 says it is hers. When Modesty is about to be punished, the Obscurus kills Mary Lou and her eldest daughter Chastity. Graves arrives, and after Credence leads him to Modesty, who he assumes is the Obscurus's host, he dismisses Credence as being a Squib and refuses to teach him magic as he had previously promised. Credence reveals he is the real host, having lived longer than any other host due to the intensity of his magic. In a fit of rage, Credence transforms and attacks the city.
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