The series begins with the execution of Gold Roger, a man known as the King of the Pirates (�µ��≥�王 Kaizoku≈�^?). Just before his death, Roger announces that his treasure, the One Piece (�≤�®�§�™ぎの�§�秘宝 (ワ�≥ピース) Wan Pƒ�su^?), will be up for the taking, causing the Great Pirate Era (�§��µ��≥�時�£ Dai Kaizoku Jidai^?) to begin. As a result, countless pirates set out to the Grand Line to look for the treasure.

Twenty-two years have passed since Roger's execution, and Monkey D. Luffy, a young pirate inspired by "Red-Haired" Shanks, has since set off on a journey from the East Blue to succeed Roger and find the treasure. He organizes and leads a nine-member crew named the Straw Hat Pirates. Each crew member Luffy encounters eventually become his close friends, including the swordsman Roronoa Zoro, the navigator and thief Nami, the sniper Usopp, the womanizing chef and martial artist Sanji, the doctor and anthropomorphized reindeer Tony Tony Chopper, the archaeologist Nico Robin, the cybernetic shipwright Franky, and the musician skeleton Brook.

The crew crosses paths with diverse villains, such as Buggy the Clown, many of the Seven Warlords of the Sea, the Navy, who place bounties on Luffy's, Zoro's, and eventually the rest of the crew's heads, and Arlong, a fishman and member of the former Sun Pirates. They encounter Baroque Works, the crime syndicate responsible for a civil war in the desert kingdom of Alabasta, along with fellow pirate Blackbeard, whose dream is also to become the King of the Pirates. The crew also confronts Eneru, the ruler of the floating island Skypiea. Later, the crew meets the navy admiral Aokiji, who reveals that Robin was involved in searching for Poneglyphs, stones with markings left by an ancient civilization. The crew also encounters Cipher Pol No. 9, the intelligence agency responsible for the destruction of Robin's homeland, who causes the pirates to declare war on the World Government. After an epic battle at Enies Lobby, the crew defeats CP9 - saving Robin and avenging the lives lost in the destruction.

Some time later, the crew prepares to sail off to the New World, the second half of the Grand Line. The crew eventually gets separated during a battle at the Sabaody Archipelago. At the same time, the navy sentences Luffy's older brother and Gol D. Roger's son Portgas D. Ace to be executed, and hold a war against a group of pirates led by Whitebeard. Luffy rescues Ace, but both Whitebeard and Ace are killed in the ensuing chaos. Later, Luffy and the crew undergo rigorous training regimens, some under the tutelage of prominent figures. Two years later, the crew regroups and journeys to Fishman Island to enter the New World. At the same time, a group of evil fishman pirates appear, and holds a coup d'état to decide the fate of the island, but are eventually defeated by the Straw Hats alongside Jimbei. The Straw Hats leave Fishman Island and finally reach the New World, but not before starting a feud with the legendary pirate Big Mom. Their first destination is the burning island Punk Hazard.