"Mary and The Witch's Flower" is a fantasy anime film centered on Mary Smith, a young girl staying in the countryside with her great-aunt. Feeling out of place and longing for adventure, Mary stumbles upon a mysterious flower known as the "fly-by-night," which grants her temporary magical powers. Alongside her discovery, she encounters a black cat named Tib, who leads her to a broomstick hidden in the woods. The broomstick transports her to Endor College, a prestigious academy for witches hidden in the clouds.

At Endor College, Mary is mistaken for a prodigious new student due to the flower's magic. She meets the enigmatic headmistress, Madam Mumblechook, and the eccentric scientist Doctor Dee, who oversee the school. The college is a place of wonder, filled with fantastical creatures and advanced magical technology, but it also harbors dark secrets. Mary learns that the fly-by-night flower is central to the school's experiments, which involve extracting magical essence from animals and transforming them into hybrid creatures.

As Mary explores the academy, she uncovers the truth about the flower's origins and its connection to a young girl named Flanagan, who once attended the school. Flanagan's experiments with the fly-by-night led to her disappearance, and her legacy is tied to the unethical practices at Endor College. Mary's curiosity and bravery lead her to confront Madam Mumblechook and Doctor Dee, who seek to exploit the flower's power for their own gain.

With the help of Tib, who is revealed to be a transformed boy named Peter, Mary works to thwart the school's plans and protect the magical creatures from further harm. The climax involves a daring escape from Endor College, as Mary and Peter use their wits and the remnants of the flower's magic to return home. The story concludes with Mary embracing her newfound confidence and sense of purpose, having experienced a world beyond her imagination while remaining grounded in her humanity. The film blends themes of self-discovery, ethical responsibility, and the allure of magic, creating a captivating narrative for audiences of all ages.