Located in Elko County, Wells became a natural rest area for emigrants heading west because of its open meadows and natural well water. The first written report of the area came from a pioneer's journal in 1845. Because the springs, (or "wells") are the source of the Humboldt River, the area was originally dubbed Humboldt Wells. By the 1850s and 1860s, hundreds of covered wagons passed through Humboldt Wells every year.

When the Central Pacific Railroad arrived in 1869, it, too, found Humboldt Wells to be a useful stopping point. A boxcar was brought in to serve as a freight distribution point for the railway. Later that year, the Bullshead Saloon was constructed and became the town's first commercial building. By 1871, the town had a livery stable, a hotel and a general merchandise store. In 1873, the town officially shortened its name to Wells.

Wells enjoyed modest success between 1872 and 1876, with a peak population of 300. Its businesses served miners, settlers, ranchers, and railroad employees. But two major fires–one in 1877 and the other in 1881–delivered a blow to the town's economy. Also, the town's successes and failures were linked to the booms and busts in the mining town of Cherry Creek to the south. Wells remained a major distribution point for Cherry Creek until the Nevada Northern Railway bypassed it in 1906. The town overcame this setback when the Western Pacific railroad arrived in 1908, followed by the Oregon Short Line in 1926.

In the 1940s, diesel locomotives began to replace those powered by steam engines, and Wells soon lost its status as a helper station for the Western Pacific. In the 1970s, the Oregon Short Line ceased operations, virtually ending railroading as an important element in the Wells economy.

In 2007, the population estimate in Wells was over 1,300, with ranching, tourism, and recreation as important industries. On the morning of February 21, 2008, an earthquake estimated at 6.0 northeast of Wells devastated the town's historic Front Street. Roughly twenty buildings, including the Bullshead Saloon, were damaged, some beyond repair. There were a few minor injuries.