Destroy All Humans!

In 1959, Cryptosporidium 137 first arrived on Earth to investigate the planet and search for his predecessor clone, Cryptosporidium 136, who disappeared in 1947 after Orthopox 13 sent him to Earth on a similar mission. Pox sends Crypto on a mission to harvest human brain stems (which contain a small amount of pure Furon DNA due to an encounter between Furon warriors and humans in ancient times) to prevent his species from going extinct. To accomplish his mission, he must defeat Majestic, a shadowy government organization led by a black-clad figure named Silhouette. After accomplishing this, Crypto takes over the United States by posing as the President.

Ten years have gone by since Crypto defeated Majestic and took over the American government. Orthropox 13 has died after a Soviet nuclear missile destroyed the Furon mothership. Pox has downloaded his consciousness into a personal holographic projector designed to communicate between Furons on Motherships and planet surfaces. Pox's unit, dubbed a HoloPox, allows him to communicate with, advise, and vex Crypto down on Earth. Crypto 137 has died of unknown causes, but appears in Big Willy Unleashed and Crypto 138, a clone with pure Furon DNA harvested from human brains, has taken his place as the President. Crypto 138 is the first Furon in millennia to possess genitalia, as his pure DNA has not been corrupted by radiation. When the KGB destroy the mothership and Pox, Crypto must find a way to stop them from destroying what he has worked so hard on to achieve. Along the way, he is supported by Natalya Ivanova, a rogue KGB agent whom he constantly hits on. He also comes across the Blisk, the dreaded enemy that the Furons thought they defeated in the Martian War.

Big Willy Unleashed takes place after Destroy All Humans! 2. Crypto and Pox start a fast food restaurant that serves human meat from all the people Crypto has killed harvesting more Furon DNA. Later, their rival restaurant, Colonel Kluckin' (a parody of Colonel Sanders), discovers their secret, whereupon Crypto must protect the restaurant with the Big Willy mascot mech.

Using the money earned from the Big Willy fast food franchise that Orthopox started in Big Willy Unleashed, Pox and his destructive Furon warrior minion Crypto have opened a "family friendly" casino with which they use to obtain a steady financial income and human DNA. Crypto has lost his motivation because of the death of Natalya (which was a clone with a four year lifespan), and has forgotten what it means to destroy humans. He drinks too much alcohol, watches too much television, and has ultimately become lazy. Later Crypto is attacked by mysterious cyborgs called Nexosporidium Warriors, who arrive from his own planet, which frightens both Crypto and his commander Pox. Soon Crypto finds himself face-to-face with a conspiracy from his own homeworld that, if not stopped, could destroy his entire race. In the midst of all the chaos, Crypto hears a voice in his head, telling him to go to the city of Shen Long. Later, Crypto, while in Sunnywood, is shot in the neck, faints, and then wakes up in a Kung Fu monastery where he is greeted by a Furon martial arts expert known as The Master. The Master beseeches him to submit to his tutelage, and train in mind and firepower, to help him defeat these new threats. Now Crypto is about to go down the path to enlightenment, shape his own destiny, and uncover who is behind this frightening conspiracy.

The franchise intellectual property (IP) holder, THQ, went bankrupt on December 19, 2012 and its many IPs were subsequently sold off. On April 22, 2013, it was announced that in a $4.9 million deal with THQ, Nordic Games now known as THQ Nordic purchased the rights to Destroy All Humans! among other IPs.[11] On their official Twitter account the company claimed: "We are thinking about what to do next with it."[12] In June 2016, Reihard Pollice, Nordic Games' product development director and executive producer, stated, "there are a few options we are evaluating now. Hope to get started on one of these soon."[13] In late 2016, the PlayStation 2 versions of Destroy All Humans! and Destroy All Humans! 2 were released on PlayStation 4 as part of the PS2 Classics lineup (a selection of PS2 games emulated on PS4, rendered at 1080p with additional features such as trophy support and remote play).[1][14] In 2018, the Xbox version of Destroy All Humans! was added to the Xbox One's backwards compatibility catalog.[15]

On June 7, 2019, THQ Nordic announced a remake of Destroy All Humans! via a reveal trailer shown at E3. The trailer was set to the 2001 song "Ich will" by Rammstein and featured Crypto and the townsfolk singing along to the lyrics. The remake was developed by Black Forest Games and released on July 28, 2020 for Microsoft Windows, PlayStation 4, Xbox One and Stadia.[16]