In the fictional town of Cheesebridge, Norvenia during the Victorian era, rumors abound that subterranean trolls known as Boxtrolls for the cardboard boxes they wear, kidnap and kill young children; wherefore Pest exterminator Archibald Snatcher strikes a deal with the city's mayor Lord Portley-Rind, to exterminate every Boxtroll in exchange for membership in the city's cheese-loving council called the White Hats despite the fact that he is allergic to cheese.
In actuality, the Boxtrolls are peaceful, and emerge from underground at night to scavenge for discarded items with which to make useful inventions. A human boy named Eggs lives among them, cared for by a Boxtroll named Fish. As Eggs grows up over ten years, he becomes dismayed by the disappearing Boxtrolls seized by Snatcher. When Lord Portley-Rind's daughter Winnie notices Eggs with two Boxtrolls, Snatcher captures Fish whereupon Eggs sneaks to the surface to find him, and emerges in an annual fair to commemorate the disappearance of the "Trubshaw Baby", presumed killed by Boxtrolls. Disgusted by the town's inaccurate portrayal of the creatures, he follows Winnie, and after a brief exchange, asks her directions to Snatcher's headquarters, located at an abandoned factory, where Eggs rescues Fish; but they are caught in the escape. Snatcher recognizes Eggs as the Trubshaw Baby and reveals that all the captured Boxtrolls are building him a machine. Winnie, who covertly followed Eggs, overhears this exchange; whereupon she, Eggs, and Fish escape from Snatcher and take shelter in the Boxtrolls' caves, where Fish explains that Eggs' father had given him to them to keep him from Snatcher, and Winnie agrees to help Eggs tell Portley-Rind the truth. At a ball held to commemorate the purchase of a giant cheese wheel called the Briehemoth, Eggs tries to confront Portley-Rind, but inadvertently knocks the cheese into a river. Eggs announces himself to the party as the Trubshaw Baby, but no one believes him.
Eggs tries to persuade the remaining Boxtrolls to flee for their own safety; and Snatcher digs into the caves and captures them all. Eggs awakens to find his father, Herbert Trubshaw, a prisoner beside him. He sees the Boxtrolls stacked in a crusher and begs them to run; whereupon they abandon their boxes to the crusher. Snatcher drives his machine to Lord Portley-Rind's house, shows him the flattened boxes as proof of the Boxtrolls' extinction and demands Portley-Rind's white hat (his symbol of office) in exchange for the last (actually Eggs disguised). The Boxtrolls and Herbert free Eggs, and Snatcher tries to take Portley-Rind's hat by force, but Eggs, Herbert, and the Boxtrolls disable the machine. The adversaries are thrown clear and land on the recovered Briehemoth, where Snatcher's allergy to cheese expands him into an enormous size. He forces Lord Portley-Rind to give up his hat in exchange for Winnie's safety; but explodes upon consumption of an aged cheese. Thereafter the townspeople co-exist peacefully with the Boxtrolls. Winnie tells the tale of Snatcher's end to a crowd, while Eggs and Fish drive off in one of Herbert's contraptions.
- Isaac Hempstead-Wright as Eggs , an orphaned human boy raised by the Boxtrolls.
- Max Mitchell as Baby Eggs
- Elle Fanning as Winnie Portley-Rind , Eggs's first human friend and the daughter of Lord Portley-Rind and Lady Portley-Rind.
- Ben Kingsley as Archibald Snatcher, a ruthless and cunning pest exterminator
- Toni Collette as Lady Portley-Rind, Winnie's mother.
- Jared Harris as Lord Portley-Rind, Winnie's father and leader of the White Hats.
- Nick Frost as Mr. Trout, Snatcher's corpulent, bumbling, yet intellectual henchman.
- Richard Ayoade as Mr. Pickles, Snatcher's spindly, well-meaning but misguided henchman.
- Tracy Morgan as Mr. Gristle, Snatcher's diminutive and maniacal henchman.
- Simon Pegg as Herbert Trubshaw, a brilliant inventor and Eggs's father.
- Dee Bradley Baker as Fish , Wheels, and Bucket, three Boxtrolls.
- Steve Blum as Shoe and Sparky, two Boxtrolls.
- Nika Futterman as Oil Can and Knickers, two Boxtrolls.
- Pat Fraley as Fragile and Sweets, two Boxtrolls.
- Fred Tatasciore as Clocks and Specs, two Boxtrolls.
- Maurice LaMarche as Sir Langsdale
- James Urbaniak as Sir Broderick, Male workman #1, Male workman #2
- Brian George as Boulanger, Male aristocrat
- Lori Tritel as Female aristocrat
- Laraine Newman as Female townsfolk #1, Female townsfolk #2
- Reckless Jack as Background boy