- "It is a historical fact: Sharing the world has never been humanity's defining attribute."
- ―Professor X
Humans, scientifically known as Homo sapiens, are the dominant species on Earth and the evolutionary predecessor to mutants.
En Sabah Nur, the first recorded mutant in history, claimed that he was responsible for facilitating the rise and fall of human civilizations. He ruled over the Nile Valley during 3600 BCE, but was ultimately entombed for millennia by humans who saw him as a false god. 
In the centuries to follow, humans developed advanced technology that they used to wage war against each other. The advent of the nuclear age was responsible for accelerating the birth rate of mutants in the 20th century, a phenomenon that was largely unknown to the world. In 1962, a mutant supremacy group known as the Hellfire Club sought to orchestrate a nuclear war between the United States of America and the Soviet Union, which would have caused the extinction of humankind and ensured that mutants would be the dominant race on Earth. Their plans were foiled by an opposing mutant group known as the X-Men. Despite the X-Men's heroic efforts, the governments of the world began to perceive mutants as a threat to humanity. 
As a response to the emerging threat that mutants posed to humankind, Dr. Bolivar Trask came up with the idea of Sentinels: machines with the ability to identify and eliminate mutants. He was assassinated in 1973 by the mutant known as Mystique, prompting the United States Government to move forward with the Sentinel program. As Trask Industries was using Mystique's own DNA to advance the Sentinels, tension between humans and mutants began to grow over the decades. 
By the 21st century, anti-mutant sentiment was widespread in the U.S. Military scientist William Stryker used it as an opportunity to kidnap Professor Charles Xavier, a telepathic mutant who oversaw a school for young mutants. After constructing a replica of the computer Cerebro, Stryker brainwashed Xavier into using the machine to telepathically kill the world's mutant population. Magneto, leader of the Brotherhood of Mutants, was able to trick Xavier into redirecting his psychic attack onto the humans instead, but the X-Men was able to stop the professor from causing any lasting damage.