Tombstone was one of the most lawless mining camps in the American West and had its share of criminal elements, but the Cochise County Cowboys were the most infamous. Originally working as ranchers or cowhands, this group of relatives and acquaintances quickly turned to a life of crime. They were so infamous that they are one of the reasons we use the term "cowboy" today. Back then, however, calling an honest rancher a "cowboy" was an insult.

On the evening of March 15, 1881, three Cochise County Cowboys attempted to rob a Kinnear & Company stagecoach carrying $26,000 in silver bullion (about $689,000 in today's dollars), en route from Tombstone to Benson. Near Drew's Station, just outside Contention City, the popular and well-known driver Eli "Budd" Philpot and a passenger named Peter Roerig were both shot and killed.

Wyatt is often erroneously regarded as the central figure in the shootout, but his brother Virgil was Tombstone town marshal and Deputy U.S. Marshal that day and had far more experience as a sheriff, constable, and soldier in combat. Together with his brothers, Virgil pursued the suspected murderers, setting off a chain of events that would culminate in the famous gunfight.

After pursuing the Cowboys for over 400 miles (640 km), they could not obtain fresh horses and were forced to give up the chase.

On June 2, 1881, Wyatt offered an unknown sum of money to Ike Clanton if he would provide information leading to the capture or death of the stage robbers. According to Wyatt, Ike was initially interested, but the plan fell apart when Ike began to worry that word of his cooperation had leaked, threatening to compromise his standing with the Cowboys.

At the scene of the second holdup, Wyatt discovered an unusual boot print left by someone wearing a custom-repaired boot heel. The Earps checked a shoe repair shop in Bisbee known to provide widened boot heels and were able to link the boot print to Stilwell.

After Doc Holliday kicked out his on-again, off-again mistress Big Nose Kate, Sheriff Behan, who was known to dislike the Earps and their associates, saw an opportunity and tried to exploit the situation. Along with saloon owner Milt Joyce, he plied Big Nose Kate with liquor and suggested a way to get even with Holliday. She signed an affidavit implicating Holliday in the attempted stagecoach robbery and murders. Judge Wells Spicer issued an arrest warrant for Holliday, but the charges were dropped when the Earps found witnesses who could attest to Holliday's location at the time of the crime.

Near midnight, Holliday and Ike Clanton got into a heated argument in the Alhambra Saloon. Virgil Earp arrived a few minutes later and threatened to arrest both Holliday and Clanton if they didn't stop arguing, but Ike told Wyatt the fighting talk had been going on for a long time and he intended to put an end to it, swearing "I will be ready for you in the morning."

A well-known city ordinance required McLaury to deposit his pistol upon arrival in town. When Wyatt demanded, "Are you heeled or not?", McLaury said he was not armed, but Wyatt saw a revolver in plain sight on Tom's right hip. Witnesses say Wyatt drew his revolver from his coat pocket and pistol whipped McLaury with it twice, leaving him prostrate and bleeding on the street. Saloon-keeper Andrew Mehan testified that he afterwards saw McLaury deposit a revolver at the Capital Saloon.

At around 2:00 pm, Ike's 19-year-old younger brother Billy Clanton and Tom's older brother Frank McLaury arrived in town. They had heard from their neighbor, Ed "Old Man" Frink, that Ike had been stirring up trouble in town overnight, and they had ridden into town on horseback to back up their brothers. By law, both Frank and Billy should have left their firearms at the Grand Hotel. Instead, they remained fully armed.