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In Destroy All Humans!, players assume the role of Cryptosporidium 137, a warrior and member of the Furon alien race. After centuries of warfare against inferior species using unchecked nuclear weaponry left their species impotent and without genitalia, the Furons were unable to sexually reproduce and became forced to turn to cloning as means of reproduction, as well as a process by which to achieve immortality. However, after generations of clones, the Furon DNA is degrading, and each clone is becoming less and less stable.Fortunately for the Furons, a Furon scout ship came across Earth many millennia ago while returning from destroying the Martians. The Furon spacefarers eventually bred with the ancestors of the human race for an unknown reason, inserting a strand of Furon DNA into the human gene pool. Because of this, it is revealed, each human contains a small amount of Furon DNA in their genetic code. Crypto is sent to Earth to harvest this DNA from human brain stems, locate and rescue his previous clone, Cryptosporidium-136 (referred to as his brother in the instruction manual), and spearhead a Furon invasion of Earth. The game is set up in a "sandbox" fashion. The player has a selection of weapons and mental abilities at their disposal, as well as access to Crypto's flying saucer. Destroy All Humans! implements the Havok physics engine, allowing for ragdoll effects on bodies and destructible environments.
The 1959 B-movie Teenagers from Outer Space becomes available to view once the main story campaign has been completed.
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