The contagion spread across the entire world, with the Crossed killing, raping, engaging in cannibalism and maiming for fun, with governments and military overwhelmed; friends and family butchered each other with anything they laid their hands on, and cities were turned into vast charnel houses.

Many Crossed are practically feral savages with absolutely no regard for their own self-preservation, to the point that they will gleefully mutilate themselves for the sheer thrill of it, including amputating their own limbs.

As stated by Garth Ennis: "The Crossed are people who – through infection – have given in to the absolute worst instincts that human beings can: murder, rape, torture, cannibalism, all of the most cruel and inventive kind imaginable.

Not consumed by unthinking bloodlust to the extent that many of the other infected are, they have enough intellectual wherewithal to plan ambushes and traps, and organize gangs of Crossed to assault survivor enclaves.

Major examples of such characters include Horsecock in the original series, Ashley and Ashlynne in Homo Superior, Smokey in The Quisling, the nun Aoileann in Wish You Were Here, and serial killer Beau Salt, whose journal and descendants survive to Crossed +100.

The captain mentioned that besides Smokey, he had heard rumors of a nun in England (Aoileann), twin sisters in Florida (Ashley and Ashlynne), and an autistic kid in Montreal (similar to epilepsy, apparently his autism made his brain structure different enough that the virus didn't take full hold).

The Crossed who survived that long tend to be the more rational and lucid ones who have the wherewithal to preserve themselves, use combat tactics like avoiding gunfire, use guns themselves, and setting complex ambushes.

In the original story, the infection erupts suddenly across the entire United States without warning and later spreads; a survivor says Canada tried to fortify the border "in the first week," and were unaware the virus had reached them until after that point.

The outbreak began in Yorkshire, United Kingdom: the patient zero was a man who had a psychotic breakdown and murdered his family, and the infection spread rapidly from two local policemen to the entire population of the village of Tethersby.

"[18] In the U.K., indecisiveness by Prime Minister Gordon Brown meant that a state of emergency wasn't declared until after a Sky News team found and filmed the villagers committing a mass suicide.

[19] From this point the infection spread rapidly, and the Prime Minister and his staff were moved into a secure bunker guarded by the SAS and SO1 police officers, which also doubled as a medical research centre where "Patient Zero" was placed under quarantine.

When Gordon Brown contacts the White House, the person answering (implied to be President George W. Bush) is clearly infected, confirming Washington D.C. has been overrun.

He appears to be tracking down the scientist who created the Crossed virus, an earlier version of which drove Jackson mad; this is simply a delusion of his, as he'd always been psychotic and the 'weapon' does not exist.

Issues #4-9 (Homo Superior, by Jamie Delano and Leandro Rizzo) follow individual survivors in the Everglades – Steve, a former military woman who has become cruel and sadistic after countless traumas in her past; Greg, a jaded family man who lives off the grid to get away from his dreary home life; Leon, a teenage "swamp rat" living at a fortified "base" with his domineering extended family; and the twins Ashley and Ashlynn, who fled the city after the Crossed outbreak began.

The only survivor is Philly, the young niece of town cop Lorna; she escapes by boat after being forced to kill her aunt, who was infected when a dead Crossed fell on her.

Four British Army soldiers (representing each nation of the United Kingdom) go on a suicide mission to break into Porton Down and release the biological weapons, hoping it will wipe out the Crossed but leave enough humans alive for Britain to rebuild and go on an offensive war against the infected.

Eventually, after ensuring the survival of the priest and his flock, they decide against their genocidal plan, instead blowing up the entrance of Porton Down to stop anyone from using its lethal cargo before setting off to make a final stand against the Crossed.

While hiding out with a group of survivors, he observes an imposing axe-wielding member of the Crossed, dubbed "Smokey" for his fireman's garb, noting that he seems to have much greater intelligence that allows him to lead his fellow infected (paralleling the character Big Daddy from Land of the Dead).

As his guilt grows and rumors of other "Super-Crossed" reach him (featuring a cameo of the twins from the Homo Superior arc), Oliver realizes that Smokey is far too dangerous to leave alive; especially when the Crossed reads his journal and assaults a nuclear base for its weapons.

She attempts to re-integrate with another group of survivors, but her growing insanity (represented by hallucinations of Harold Lorre from Psychopath) drives her to kill them all before returning to the crawlspace, determined to remain until she either dies or overcomes her madness.

After being drugged, gang-raped, and humiliated on the Internet while in America, Emiko channels her anger and shame into Gore Angels, an incredibly violent manga sold under a pseudonym with the help of her friend Satoshi.

Issues #50–56 (The Thin Red Line, by Ennis and Christian Zanier) reintroduce the four men from The Fatal Englishman, revealing them to have once been security for British Prime Minister Gordon Brown.

They eventually find safe haven at a woodland camp commanded by Sutter, a hardened survivalist with plans of his own that have little to do with the survival of his campmates... Issues #62–70 (by Lapham and Francisco Manna) concern Gavin Edward Land, a former police detective seeking vengeance against the people who raped and murdered his daughter.

Along with his similarly-infected assistant (and Washington's college girlfriend) Amy, he wrote the story not as an attempt to falsify history, but as a vision of the society he intends to create with his band of Crossed.

Issues #91–92 (Anti-Crossed, by Bemis and German Erramouspe) follow a group of 5 survivors – 4 men and a female author named Leigha – surviving in a barricaded comic book store as they struggle with their depleting morale and growing boredom.

Issues #93–99 (by Gage and Fernando Heinz) begins by following a band of survivors led by Cody, an opportunistic man who designed disaster shelters for the elite before stealing one for himself when C-Day hit.

When this inevitably fails (in part due to a remorseful Cody sacrificing himself to undo his own work), Smokey seeks out other Super-Crossed like himself, eventually finding the Crossed twins from the Homo Superior arc.

Teenagers and children infected in the initial outbreak were not strong enough to compete against adult Crossed at the time, so they didn't tend to survive forty years of constant fighting.

In the Tennessee region shown in Crossed: +100, major religions such as Judaism and Christianity have died out, and most people are irreligious, though there are a few survivor enclaves that still practice Islam (the comic creators stated that one of the reasons the story was set in Tennessee is due to the large Muslim population in present-day Murfreesboro; other large Muslim populations in the United States are concentrated in major metropolitan areas, which thus stood lower chance of surviving the Crossed epidemic).

Chaos unfolds as the uninfected humans seek to protect the remaining settlements in the east coast area of the US, while trying to uncover the conspiracy laid out by Salt a hundred years earlier.