The original claim to the mine was staked in 1877 by a prospector named George Warren, attracted by outcrops with the lead mineral cerussite, which often carried silver. An option on the mine was acquired in 1880 by entrepreneur Ed Reilly who raised $80,000 capital from Dewitt Bisbee to begin production. The surface pockets of cerussite were soon exhausted, but the owners found that the orebody ran 23% copper, with silver and gold as byproducts. Most mines of that era could profitably mine ore containing 3% or 4% copper, so the Copper Queen orebody was considered extraordinarily high grade. The surface oxide ore was exhausted after three or four years, but miners explored deeper and eventually found even larger orebodies.
In 1884-5 the mine was offered for sale to London investors for £350,000, but the offer was not taken up, and the mine was acquired by Phelps Dodge, which introduced a policy of racial segregation at the mine, with workers of Mexican origin not allowed to perform skilled jobs.
In the early 20th century deposits of gold and silver were also discovered in the mine.