Around 1870 more gold, silver, and lead deposits were again discovered in the Coso Range, resulting in formation of the New Coso Mining District in 1874. The settlement of Darwin was soon established and named for early explorer and prospector, Dr. Darwin French. Quickly developing into the main commercial center in the area, by the end of 1875, Darwin boasted two smelters, some 20 operating mines, a post office, graded streets, a drug store, hotel, three restaurants, the ever-present saloons, a newspaper, 200 frame houses and more than 700 residents. The Defiance Mine was the principal producer in the district, but, other profitable mines included the the Argus-Sterling, Christmas Gift, Lucky Jim, Custer, Independence, Keystone, Thompson, and the Wonder Mine.

The next year, the town continued to grow, supporting over 1,000 people, at which time, it was the largest town in Inyo County. It's Centennial Celebration on July 4, 1876 was the second largest in the county. Though the settlement had taken on an air of permanence, it was also gaining another reputation -- that of a rowdy and violent town. Because of its isolation, and distance from the county seat of Independence, gunplay, assaults, and stage robberies were common. Still, the town continued to grow, peaking at a population of about 3,500 in 1877. However, it would not continue. The following year a smallpox epidemic swept the community and a national economic slowdown hit Darwin hard. Production slowed and mine owners scaled back wages, creating more violence in the community.

In September, 1878, the the newspaper office closed its doors and the publisher, T. S. Harris, packed up the presses and headed north toward the boomtown of Bodie. He was followed by many of the miners. However, the following month, it was reported in the Independence newspaper that the town still had 200-300 people, four stores, three restaurants, five saloons, and a drug store. Six months later on April 30, 1879, a suspected arson fire began in the Darwin Hotel, which resulted in the loss of 14 businesses, including several stores, offices, the hotel, saloons, and the post office.

Though much diminished from its former self, Darwin didn't completely die. In 1880, some 85 people still called it home. In 1902; however, the post office closed briefly, but, would later reopen. 

During the early 1900's a rebirth of the mining industry occurred in southern Inyo County when copper, which had earlier been left on the dumps because it was considered worthless, began to be mined in earnest as its value had risen dramatically. In 1907 Senator Tasker L. Oddie of Nevada bought nine claims in the Darwin area, while George Nixon and George Wingfield of Goldfield, Nevada fame also took over some property. At the same time, the Lucky Jim Mine was shipping lead-silver ore to Salt Lake City smelters in Utah. Another smelter opened in nearby Keeler and during the next ten years more mines opened and older ones were re-worked. A new hotel was built, and the town began to show true signs of coming back to life. Unfortunately, in August, 1917, another fire blazed through the town which destroyed a service garage, the new hotel, a saloon and three homes. Less than a year later another fire swept down the other side of Main Street destroying more homes and businesses.