John Wesley Hardin was born on May 26, 1853, near Bonham, Texas. His parents were James Gibson "Gip" Hardin, a Methodist preacher, and Mary Elizabeth Dixson. He was named after John Wesley, the founder of the Methodist denomination. Hardin had a large family, being the second surviving son among ten children.

When he was six years old, his father moved the family to Sumpter, Texas, in 1859. There, Gip Hardin started a school that John and his siblings attended. The Hardin family had deep roots in Southern politics and were related to several notable politicians.

During the Civil War, Hardin's father became a Confederate Captain. At the young age of nine, Hardin attempted to run away from home to join the Confederate army.

Hardin struggled in school. In 1867, he had a serious conflict with another student named Charles Sloter. Sloter accused Hardin of writing graffiti that insulted a girl. When Sloter attacked Hardin with a knife, Hardin defended himself and stabbed Sloter with the knife he was using.

In 1868, at the age of 15, Hardin won a wrestling match against his uncle’s former slave. The next day, he claimed he was ambushed by the man. In an act of self-defense, Hardin shot him multiple times. After this shooting, he became a fugitive to avoid arrest, believing he wouldn't receive a fair trial in the environment of the Civil War. 

In November 1868, John Wesley Hardin, then 15 years old, became involved in his first killing. After winning a wrestling match against Major "Maje" Holshousen, an ex-slave, Hardin claimed that Maje ambushed him days later. In defense, Hardin shot Maje five times, leading to Maje’s death three days later. Hardin fled afterward, fearing he would not receive a fair trial in the Union-occupied South.

As a fugitive, Hardin continued to be involved in violent confrontations. He claimed to have killed two men, a white man and a black man, during an altercation with Union soldiers while on the run. He was also accused of various other killings during this period. In January 1870, Hardin killed Benjamin Bradley in a card game dispute when Bradley threatened him. Witnesses verified this shooting, marking another death attributed to Hardin.

In 1871, Hardin was arrested for allegedly killing Waco's city marshal but managed to escape while being escorted to trial. He claimed to have killed the officer escorting him before making his way back into hiding. The following months saw a series of violent incidents, including the deaths of several men during disputes or confrontations, further cementing Hardin’s reputation as a violent outlaw.

Hardin engaged in a number of gunfights throughout Texas and became involved in the Sutton-Taylor feud, where he killed multiple lawmen. By 1873, he was sought for the murders of a deputy sheriff and the sheriff himself, both associated with his rivals. His actions during this feud led to widespread notoriety, and law enforcement struggled to keep up with him.

In 1874, while still under the threat of arrest, Hardin allegedly killed Deputy Sheriff Charles Webb during a confrontation in Comanche, Texas. This incident resulted in a bounty being placed on his head, and he continued to evade capture despite numerous attempts to arrest him.

Hardin was eventually captured in 1877 in Florida after years of being a fugitive. He was tried and sentenced to 25 years in prison for murder but continued to maintain that the stories of his killings were often exaggerated or fabricated. While in prison, he wrote an autobiography, reflecting on his life of violence.

After serving about 17 years, Hardin was released in 1894. He attempted to start anew but soon returned to gambling and trouble with the law. By August 19, 1895, Hardin was shot dead in a saloon in El Paso by Constable John Selman during an argument. Selman claimed self-defense during his trial, but his fate after that was ultimately determined by a shootout with a U.S. Marshal while free on bail for Hardin's murder.