Born in Harlem, Luke Cage was looked down upon for being black. Willis Stryker, a neighborhood kid and mutant, was mistreated as well for his snake-like appearance. Growing up, the two became best friends, handling their adversity together. Eventually, the two turned to crime in order to take out their frustrations on the world around them. While the two had their differences, nothing came between them...until they met Reva. When Reva began showing interest in Cage, Stryker planted cocaine in his apartment and called the police. Cage was arrested and sent to jail, while Reva turned to Stryker for comfort. Their relationship was eventually cut short in a hail of bullets, as the drug pushers who the cocaine was actually meant for sought revenge. Stryker walked away unscathed, but Reva was killed.

Sent to Seagate Prison in the Florida Everglades, Cage refused to give in to the commands of the guards, and was beaten on a regular basis. Outside the prison, a war raged, as Magneto gathered the world's oppressed mutants around him and struck out against humanity. Realizing they needed more than just Sentinels and conventional weaponry, the government decided to create their own super-powered beings. For experimentation, they turned to the prison system, where Cage was offered a reduced sentence for participation in the government's super-soldier program. Eventually, Cage grew frustrated with the experimentation and broke out of jail, escaping into the Everglades. Making his way north, Cage learned of Magneto's overthrow of the world's governments, and the transformers he sent around to give those humans who wanted to be mutants the chance (assuming they possessed a latent mutation).

Eventually making it back to New York City, Cage immediately sought out Stryker. Intent on destroying Cage, Stryker killed himself with a grenade, thinking it would kill his old friend as well. As Cage walked out of the smoke, he took control of Stryker's gang, and moved them to a part of New York City known as Sapien Town. There, he began carving out a territory for his gang, taking down Cockroach Hamilton, Piranha Jones, and Hammerhead. Then one night, while pulling a heist, he ran into Hawkeye. Realizing they had something in common, Hawkeye joined Cage's gang. The two then sought out and found Iron Fist, a wanted killer, only to run into ex-C.I.A. agent Marc Spector aka Moon Knight as well. Cage and Hawkeye managed to recruit both into their organization where they were also joined by ex-S.H.I.E.L.D. agent Mockingbird.

One day, while walking around Sapien Town, Cage heard a commotion, finding his fellow humans beating a seeming-mutant. Saving the girl, he learned that while she had a cat appearance she was not, in fact, a mutant. Tigra was actually a member of the Human Resistance Movement, valued for her ability to infiltrate mutant society.

Luke Cage became the kingpin of Hell's Kitchen. He used his crime syndicate to run part of the human resistance, and had close ties to Tyrone Johnson (Cloak). Layla Miller opened Cage's eyes before anyone else in the House of M universe.