The aftermaths of both the Levely and the Raid on Onigashima, as well as the erasure of the Lulusia Kingdom, cause major shifts across the world that could lead to global war. The Straw Hat Pirates, following their Log Pose, arrive at the mysterious, futuristic island Egghead where the super genius Dr. Vegapunk resides. However, after being tipped off about Vegapunk's research into the Void Century, the World Government decides to dispatch a CP0 team to assassinate Vegapunk. Betrayal and intrigue on all sides leads to a Marine siege on the island that will escalate into an incident that will shock the world.

The Ninja-Pirate-Mink-Samurai Alliance gather their forces in Wano Country and prepare for their inevitable clash against the Beasts Pirates. The history of Kozuki Oden and his ties to Wano Country, Whitebeard and Gol D. Roger are revealed, and the Alliance assaults Onigashima to take down the allied forces of Kaidou and Big Mom once and for all. The resulting battle, as well as the events during the recent Levely, cause the world to go through dramatic changes.

The Straw Hat Pirates' actions against the Big Mom Pirates are revealed to the world. Luffy's group is on its way to Wano Country while the Revolutionary Army prepares for their next move. Meanwhile, royalty across the globe gathers for the Reverie, without knowing that a shadow-like figure is pulling the strings of the World.

Luffy, Nami, Chopper, Brook, and the minks Pekoms, Pedro, and Carrot head to Whole Cake Island, where Big Mom of the Four Emperors resides. Nicknamed the Sanji Retrieval Team, the group seeks to rescue their crewmate Sanji from his arranged marriage with Charlotte Pudding, set up to finalize a political alliance between the Charlotte Family and the Vinsmoke Family. However, during their operation, they become involved in a plot to assassinate Big Mom herself.

After defeating Doflamingo, the Straw Hats, Trafalgar Law, Kin'emon, and Kanjuro arrive on Zou, in order to reunite with Sanji and the others. However, they discover that Sanji has been swept up in a set of personal and political entanglements and that Zou has been subjected to a siege by Jack of the Beasts Pirates.

A sequence of unexpected events shakes the world order, and Doflamingo proves to be a challenge that even some of the strongest warriors cannot overcome.

The Straw Hat Pirates and Trafalgar Law, together with Kin'emon, Momonosuke and the captured Caesar Clown, travel to Dressrosa with the goal of taking down the nation's king, Warlord of the Sea Donquixote Doflamingo. However, they soon set into motion a series of world-changing events, as their actions interact unexpectedly with those of larger forces at play.

Upon finally entering the New World, the Straw Hat Pirates immediately receive a distress call from residents of Punk Hazard, who state that a samurai is attacking them. Without hesitation, Luffy sets out to the blazing island, with Vice Admiral Smoker hot on his tail. On the supposedly death-ridden and empty island, the Straw Hats soon must contend with both the G-5 Marines, led by Vice Admiral Smoker, and the mad scientist Caesar Clown, whose deadly experiments must be stopped.

The Straw Hat Pirates finally arrive at Fishman Island. There, the crew learn the history of Fisher Tiger and the ongoing discrimination between humans and fishman, while the New Fishman Pirates plot to overtake Ryugu Kingdom and make fishman be recognized as the supreme race.