The Comedian is Edward Blake. The Comedian was based on the Charlton Comics character Peacemaker, with elements of the Marvel Comics spy character Nick Fury added. Moore and Gibbons saw The Comedian as "a kind of Gordon Liddy character, only a much bigger, tougher guy". Moore has observed elsewhere that the character's pseudonym was inspired by Graham Greene's novel 'The Comedians'. Gibbons went with a Groucho Marx-style appearance (moustache and cigar) for the Comedian in his design, deciding that the "clown" look had already been appropriated by DC Comics' Joker. His costume itself was noted by Gibbons as being particularly problematic, he was initially designed with a more militaristic costume which was later dropped for a black leather outfit with a "rapist mask". He believes that humans are savage in nature, and that civilization can never be more than an idea. He therefore chooses to become a mockery of society, fighting and killing without reservation.

Blake's murder, which takes place shortly before the story begins in 1985, sets the plot of Watchmen in motion. The character appears throughout the story in flashbacks and aspects of his personality are revealed by other characters. Richard Reynolds described The Comedian as "ruthless, cynical, and nihilistic, and yet capable of deeper insights than the others into the role of the costumed hero". Nicholas Michael Grant said the Comedian is "the only character in the Watchmen universe who is almost totally unlikeable." Paige MacGregor said Comedian's unusual appeal to women was due to "the willingness of Sally Jupiter [...] to have consensual sex with [him] after he tried to rape her" and because of a later moment in which he breaks down and shows his "innate humanity".

He and Doctor Manhattan are the only two superheroes to be government-sanctioned after the Keene Act banning costumed vigilantism is passed.

In the Watchmen film he is played by Jeffrey Dean Morgan.

Physicist Dr. Jonathan "Jon" Osterman was transformed into a blue-skinned god-like being after he was accidentally disintegrated in an "Intrinsic Field Subtractor" in 1959, when he became trapped in the chamber while attempting to retrieve a watch inside it. Within a few months, his disembodied consciousness managed to reconstruct a physical body for itself, after several earlier attempts, assisted in part (it is implied) by his childhood training in watch repair and a solid understanding of precision assembly and disassembly. He is immediately pressed into service by the United States government, who gives him the name Doctor Manhattan, after the Manhattan Project. He is the only character in the story who possesses real superpowers. Though he dabbles briefly in crime-fighting, his greatest influence is to grant the U.S. a strategic advantage over the Soviet Union during the Cold War, with his most significant action taking place after he is personally asked by President Richard Nixon to intervene in the Vietnam War, leading to an unqualified victory for the U.S. with the defeat of North Vietnam and the Vietcong, preventing the collapse of the Saigon government and allowing the eventual annexation of Vietnam as the 51st state. Since he works for the U.S. government, he is exempt from the provisions of the Keene Act, but spends much of his time doing advanced technology research and development and physics research. He is single-handedly responsible for the shift to electric-powered vehicles (by synthesizing the needed elements and chemicals himself) and Veidt credits him with causing a huge leap forward in myriad areas of science and technology. After the death of his father in 1969, he does not bother to conceal his original name and is repeatedly addressed or referenced as "Jon" or "Dr. Osterman".

Doctor Manhattan was based on Charlton's Captain Atom, who in Moore's original proposal was surrounded by the shadow of nuclear threat. However, the writer found he could do more with Manhattan as a "kind of a quantum super-hero" than he ever could have with Captain Atom. Moore sought to delve into nuclear physics and quantum physics in constructing the character of Dr. Manhattan. The writer believed that a character living in a quantum universe would not perceive time with a linear perspective, which would influence the character's perception of human affairs. Moore also wanted to avoid creating an emotionless character like Spock from Star Trek, so he sought for Dr. Manhattan to retain "human habits" and to grow away from them and humanity in general. Gibbons had created the blue character Rogue Trooper, and explained he reused the blue skin motif for Doctor Manhattan as it resembles skin tonally, but has a different hue. Moore incorporated the color into the story, and Gibbons noted the rest of the comic's color scheme made Manhattan unique. The blue skin color is explained as being a result of Cherenkov radiation. Moore recalled that he was unsure if DC would allow the creators to depict the character as fully nude, which partially influenced how they portrayed the character. Gibbons wanted to tastefully depict Manhattan's nudity, selecting carefully when full frontal shots would occur and giving him "understated" genitals — like a classical sculpture — so the reader would not initially notice it. Dr. Manhattan's forehead is marked with the atomic structure of hydrogen, which he himself put on, declining a helmet with the atom symbol.

In the Watchmen film, Doctor Manhattan is a CGI character modeled after Greg Plitt with motion capture and facial performance provided by Billy Crudup. Crudup also plays the pre-transformation Jon Osterman.

The second Nite Owl is Daniel Dreiberg, a retired, out-of-shape superhero who uses owl-themed gadgets, in a manner which led Dave Gibbons to consider him "an obsessive hobbyist... a comics fan, a fanboy." Nite Owl was based on the Ted Kord version of the Charlton superhero Blue Beetle. Just as Ted Kord had a predecessor, Moore also incorporated an earlier adventurer who used the name "Nite Owl", the retired crime fighter Hollis Mason, into Watchmen. While Moore devised character notes for Gibbons to work from, the artist provided a name and a costume design for Hollis Mason he had created when he was twelve. Richard Reynolds noted in Super Heroes: A Modern Mythology that despite the character's Charlton roots, Nite Owl's modus operandi has more in common with the DC Comics character Batman. According to Geoff Klock, his civilian form "visually suggests an impotent, middle-aged Clark Kent." The second Nite Owl is another Crimebusters vigilante who has not revealed his identity in the post-Keene Act era throughout the novel.

In the 2009 Watchmen film he is played by Patrick Wilson, who put on 25 pounds in between the filming of his flashback scenes and the 1985 scenes, showing the physical decline of his character.

Adrian Veidt was formerly the superhero Ozymandias, drawing inspiration from his hero Alexander the Great and the Egyptian pharaoh Ramesses II, for whom he is named. In the same way as doctor Manhattan is a "god" figure, Ozymandias represents Friedrich Nietzsche's ideal of the Ubermensch from which Superman was named. He inherited a fortune, but gave it away to see if he could be a success by himself. Ozymandias traced Alexander's path himself. He is the story's main antagonist. At the start of Watchmen he has retired to devote his attention to the running of his own enterprises. Ozymandias was directly based on Peter Cannon, Thunderbolt, whom Moore had admired for using his full brain capacity as well as possessing full physical and mental control. Veidt is believed to be the smartest man on the planet, even capable of outsmarting Dr. Manhattan. His combination of intelligence and highly advanced fighting skills makes him perhaps the most feared and dangerous of the mortal Crimebusters. He was even able to catch a bullet fired at him. He is often accompanied by his genetically-engineered lynx, Bubastis. Richard Reynolds noted that by taking initiative to "help the world", Veidt displays a trait normally attributed to villains in superhero stories, and in a sense he is the "villain" of the series. Gibbons noted "One of the worst of his sins [is] kind of looking down on the rest of humanity, scorning the rest of humanity." In 2008, he was ranked number 10 on the Forbes Fictional 15. Wizard magazine also ranked Ozymandias as 25th greatest villain of all time and IGN ranked him as 21st Greatest Comic Book Villain of All Time.