Hawthorne was established in 1881 as a freight depot and repair station for the Carson and Colorado Railroad, which was in the process of extending its track to the boomtown of Candelaria. The town got off to a slow start because no mines of significant value were discovered in the area. Its economy experienced a small boost in 1883, when the seat of Esmeralda County was moved from Aurora to Hawthorne. The railroad sustained the town through the end of the nineteenth century, and it supported a population of 436 in 1900.

The discovery of silver in Tonopah led to modifications in the railroad that had a negative effect on Hawthorne. The Southern Pacific Railroad, which had acquired the Carson and Colorado in 1900, was under pressure to relieve congested supply lines that were the result of the Tonopah mines. After building a standard-gauge track that ran along the east side of Walker Lake in 1905, the railroad decommissioned the narrow-gauge line that ran through Hawthorne. All shops and railroad repair facilities were moved from Hawthorne to the new town of Mina to the southeast. Soon after it lost its railroad, the town lost the other important component of its economy. In 1907, Esmeralda's county seat was moved from Hawthorne to Goldfield.

These losses made Hawthorne's future look bleak. But in 1906, a small discovery of silver-bearing rock outside of town led to a revival. By 1909, the Lucky Boy mine was showing great promise, with Hawthorne serving as its trading center. Then, in the 1911 legislative session, arguments were made that Goldfield was too far away from Hawthorne to act as an effective county seat. As a result, Mineral County was formed out of Esmeralda's top half, and Hawthorne was named as its seat. But as the Lucky Boy mine faded and other mining towns flourished, Hawthorne's future was again uncertain. In 1920, the population had fallen to 244, and a fire destroyed most of the town in 1926.

At about the same time, an ammunition depot exploded in New Jersey, leading the U.S. government to look for a place to store weapons in a less populous area. Tasker L. Oddie, a U.S. Senator from Nevada and a member of the Naval Affairs Committee, was a key figure in the decision to make Hawthorne the final choice for the facility. Construction of the Hawthorne Naval Ammunition Depot began in 1929, and by 1930, Hawthorne's population had grown to 757. The complex became the largest weapons storage facility in the United States, encompassing over 230 square miles.

The government began to rapidly expand the ammunition depot in 1940 as concern grew over the United States' potential involvement in World War II. Hawthorne's population mushroomed after the country entered the war, and the government built a nearby community called Babbitt to house employees. At one point during the war years, Hawthorne and Babbitt supported a population of 13,000. The population receded with the end of the war, but later surged during the Korean and Vietnam conflicts.

During the following decades, the houses in Babbitt were dismantled or moved to other communities, and today, there is little left of the town. In 1977, the Department of Defense ordered the Navy to turn the ammunition depot over to the Army. The government turned the facility over to a private contractor in 1980.

A large number of African Americans came to work at the ammunition depot in the 1940s and 1950s, and endured a segregated society for a longer time than those in other Nevada communities. Public places such as movie theatres segregated their patrons, and at least one major casino and restaurant, The El Capitan, refused service to African Americans. The town did not integrate until the passage of the Civil Rights Act of 1964.

Since 1980, the Hawthorne Army Depot has reduced the number of its employees. In 2005, the Defense Department's Base Realignment and Closure Commission (BRAC) threatened to shut down the facility, but it was later removed from the closure list.

Hawthorne survives as the seat of Mineral County, with recreation and tourism as important industries because of fishing opportunities at nearby Walker Lake. However, the future of angling at the lake is uncertain as upstream diversions and numerous droughts have caused its waters to recede. In 2000, the town's population was 3,311.