It's Connecticut in the 1960s and Arthur (FREDDIE HIGHMORE) is an inquisitive and inventive boy who lives with his grandmother, Granny (MIA FARROW) while his parents work in a distant city. Arthur is enamored with the amazing expeditionary stories penned by his long-lost grandfather, Archibald (RON CRAWFORD), including when he discovered the Minimoys, a tribe of tiny people. Arthur gets his chance to meet them when a developer informs his grandmother that if she can't pay the bills, the farm will become his. Knowing that his grandfather wrote about African rubies he buried somewhere on their land, Arthur sets out to find them, a quest that leads to instructions about how to travel to the Seven Kingdoms of the Minimoys.
Racing against time, Arthur is miniaturized and ends up in their world that exists right there on their farm, with only 36 hours to find the rubies and return before the magical portal closes for the next 1,000 days. There, he meets the troll-like Minimoys, including Miro the wizard (voice of HARVEY KEITEL), the boyish but 300-year-old Betameche (voice of JIMMY FALLON), and his teenage-like sister Princess Selenia (voice of MADONNA) who will turn 1,000 in two days and thus replace her father, the King (voice of ROBERT De NIRO), as ruler of their land.
Her future rule depends on how she'll be able to deal with the evil Maltazard (voice of DAVID BOWIE) and his villainous son Darkos (voice of JASON BATEMAN) who rule over Necropolis, the forbidden kingdom. Maltazard wants to reign supreme over the other six kingdoms, but Arthur informs the Princess and everyone else that if he doesn't return with the missing rubies, Maltazard won't matter since all of their lands will be destroyed along with the family farm. Accordingly, Arthur, Princess Selenia and Betameche set out to find the stones, encountering colorful characters such as Rastafarian-like Max (voice of SNOOP DOGG) and Koolomassai (voice of ANTHONY ANDERSON) along the way, all while dealing with Maltazard and his minions who try to stop them.