The world of One Piece is populated by humans and many other races, such as dwarves, fish-men, and giants. It is covered by two vast oceans, which are divided by a massive mountain range called the Red Line; The Grand Line, a sea that runs perpendicular to the Red Line, further divides them into four seas: North Blue, East Blue, West Blue, and South Blue. Surrounding the Grand Line are two regions called Calm Belts, similar to horse latitudes, which experience almost no wind or ocean currents and are the breeding ground for huge sea creatures called sea kings. Because of this, the calm belts are very effective barriers for those trying to enter the Grand Line.

However, navy ships, members of an intergovernmental organization known as the World Government, are able to use a sea-prism stone to mask their presence from the sea kings and can simply pass through the calm belts. All other ships are forced to take a more dangerous route, going through a mountain at the first intersection of the Grand Line and the Red Line, a canal system known as Reverse Mountain. Sea water from each of the four seas runs up that mountain and merges at the top to flow down a fifth canal and into the first half of the Grand Line, called Paradise because how it compared to the second half. The second half of the Grand Line, beyond the second intersection with the Red Line, is known as the New World.

Further information: List of One Piece characters

The series focuses on Monkey D. Luffy, a young man made of rubber, who, inspired by his childhood idol, the powerful pirate Red-Haired Shanks, sets off on a journey from the East Blue Sea to find the mythical treasure, the One Piece, and proclaim himself the King of the Pirates. In an effort to organize his own crew, the Straw Hat Pirates, Luffy rescues and befriends a pirate hunter and swordsman named Roronoa Zoro, and they head off in search of the titular treasure. They are joined in their journey by Nami, a money-obsessed thief and navigator; Usopp, a sniper and compulsive liar; and Sanji, a amorous but chivalrous cook. They acquire a ship, the Going Merry, and engage in confrontations with notorious pirates of the East Blue.

As Luffy and his crew set out on their adventures, others join the crew later in the series, including Tony Tony Chopper, an anthropomorphized reindeer doctor; Nico Robin, an archaeologist and former Baroque Works assassin; Franky, a cyborg shipwright; Brook, a skeleton musician and swordsman; and Jimbei, a fish-man helmsman and former member of the Seven Warlords of the Sea. Once the Going Merry is damaged beyond repair, Franky builds the Straw Hat Pirates a new ship, the Thousand Sunny, Together, they encounter other pirates, bounty hunters, criminal organizations, revolutionaries, secret agents, and soldiers of the corrupt World Government, and various other friends and foes, as they sail the seas in pursuit of their dreams.