The area around what is now Jerome was mined for silver and copper since the Spanish colonial era when Arizona was part of New Spain.
A mining camp named Jerome was established on the side of Cleopatra Hill in 1883. It was named for Eugene Murray Jerome, a New York investor who owned the mineral rights and financed mining there. Eugene Jerome never visited his namesake town. Jerome was incorporated as a town on 8 March 1889. Local merchant and rancher William Munds was the first mayor. The town housed the workers of the nearby United Verde Mine, which was to produce over 1 billion dollars in copper, gold and silver over the next 70 years.
Jerome became a notorious "wild west" town, a hotbed of prostitution, gambling, and vice. On 5 February 1903, the New York Sun proclaimed Jerome to be "the wickedest town in the West".
In 1915 the population of Jerome was estimated at 2,500.