"Curse your 'bloodlines' then...!! You people were born as lowly trash, destined to be controlled!! You humans and I are completely different!"While many of the baddies from One Piece range from mere insensitive jerks to all-out line-crossing assholes, there are a few villains who put all others to shame. Characters are listed by the arcs where they have the most impact; they may have appeared earlier or appear later.
—Donquixote Doflamingo, manga Chapter 790
- Kuro Arc: The titular Captain Kuro, one of the earliest villains, was once a feared pirate known as Kuro of the Thousand Plans. Wearied from an existence on the run from bounty hunters and the Marines, Kuro hatched a scheme: he slaughtered every marine on a ship, save one, and had his right hand man Jango the Hypnotist hypnotize a crewmember and the surviving marine to make them think they were Captain Kuro and his captor, leading to the execution of the fake Kuro. Kuro traveled to Sugar Island where he became the butler of a kind, sickly girl named Kaya under the name "Klahadore", looking after her after her parents died. Kuro plotted to have his former crew arrive and slaughter the island while he'd have Kaya hypnotized to write him as the beneficiary of her will before he murdered her. After Kaya bought him a gift of new glasses, Kuro heartlessly crushed them and attempted to kill her other servant Merry. When Kaya said she'd have just given him the money, he admitted he just wanted her dead for the sake of his ego. Kuro was also planning on killing his crew to complete his disappearance and when fighting Luffy, used an attack that led to them being nearly massacred by him. Though an early villain, Kuro was easily one of the most vile.
- Impel Down Arc: Shiliew/Shiryu of the Rain is the psychotic former Head Jailer of the titular prison. He murders dozens, if not hundreds, of prisoners just for fun, claiming them to be "just trash" and making the actual Head Jailer Magellan completely disgusted. When freed, he cuts down his former workmates multiple times with not regard for them, sides with Blackbeard, and thinks of betraying him too if he does not succeed in stealing Whitebeard's power. It's pretty clear he has no empathy and loyalty for anyone but himself.
- Marineford Arc: Admiral Akainu (real name Sakazuki) makes his debut by ordering his subordinates to blow up a ship of evacuees that the Marines had promised to spare. Later on, he brutally murders anyone who tries to flee from the battle at Marineford. He also tried to murder Coby when the latter and calls out everyone for their violence, and the two are theoretically on the same side. He moves the series into Darker and Edgier territory by causing the first major present-day story death (Portgas D. Ace, who sacrifices himself to safe Luffy). To give an idea how bad he is, when Sengoku stepped down and Aokiji had to fight Akainu for the position, when Aokiji ultimately lost, he left the Marines rather than serve under him.
- Fishman Island Arc: Hody Jones is a Fishman who takes Arlong's Fantastic Racism and turns it Up to Eleven. He's not only more brutal, more racist, more treacherous, and more cruel, but he pulls a reversal on Arlong's sole Pet the Dog moment: whereas Arlong was mortified when Luffy used a Fishman as a Human Shield, Hodi himself uses a Fishman as a human shield against an attack. One of Arlong's former crew, Hatchi, stated that, while Arlong was a bastard through and through, he'd never hurt a Fishman no matter what. Hody, on the other hand, is known for killing any who talk to or know them. When he tries to take over Fishman Island, part of his plan is to execute all who had signed Queen Otohime's petition. This means that he's planning to murder thousands of its residents. He already killed Otohime and framed the human he hired to burn the petitions in the first place as part of this plan, and got cocky enough to brag about it in front of all Fishman Island.
- Punk Hazard Arc: Caesar Clown has convinced people he's a kind master and scientist who just wants to help people. The truth is that Caesar is violently jealous of his former associate Dr. Vegapun and once took that frustration out by blowing up an island. In the present, Caesar keeps multiple children in his lab with promises to cure them of their sickness, and gives them candy to help them. The "candy" is in truth an addictive drug to keep them enslaved to him, and his experiments will cause their deaths in five years. He shows no remorse, laughing that he can always get more children. Caesar also saved pirates and sailors from death, but uses them as test subjects as well and turns them against their captain who was just trying to save them from Caesar. When his back is against the wall, Caesar has no compunction killing these men with a poison gas he unleashes in an attempt to kill Luffy. Caesar has no loyalty to anyone but himself and his psychotic ego combines scientific drive with a sadist's streak a mile long.
- Dressrosa Arc: Donquixote Doflamingo (the boss of the aforementioned Caesar Clown, incidentally) is steadily revealed as the epitome of selfish egomania whose own brother describes as having been born an evil madman, despite his servants' Undying Loyalty towards him. In the guise of "Joker," Doflamingo is a mover and shaker in the criminal underworld where he participated in a slave trade for the pleasure of the corrupt Celestial Dragons. When conquering his old kingdom of Dressrosa, Doflamingo enslaved the people by turning many into toys and making their loved ones forget them, and framing the good-hearted King Riku Dold by forcing him to attack the people he loved so much to make Doflamingo a "hero" for removing him. It is also revealed he planned to brainwash Trafalgar Law into being his loyal slave who would gladly trade his life to bring Doflamingo immortality, executing his own brother Rosinante when Rosinante tried to save Law. In his crowning moment of evil, Doflamingo attempted to massacre everything in Dressrosa, his own men included, gleefully proclaiming he would just find a new country and "family." Even upon his defeat, all Doflamingo cares about is seeing the news so he can appreciate the chaos the world is thrown into by recent events.