Like countless cities in the American West, Reno was founded because of the establishment of nineteenth-century railroad networks. However, Reno's network did much more than simply inaugurate the town; it fostered the city's unique enterprises that popularized Reno in the following decades. The railroad was the force that not only allowed Reno to benefit economically from transportation and commerce rather than mining (as with other northern Nevada railroad towns) but it also fed the city's lucrative "sinful industries"—divorce and gaming, in particular—and helped them prosper by bringing people from all over the country to Reno. Essentially, the railroad became Reno's lifeline, promoting commerce by freight and passenger trains, ensuring that Reno would not be dependent on boom and bust industries like most other towns in the state.

Surveyors for the Central Pacific Railroad arrived in the valley as early as 1863, but by March 1868 railroad officials had selected a site for the station on the north side of the Truckee River near an important river crossing owned by Myron C. Lake (Lake's Crossing). This favorable locale was both distant from the hills to the west (an important factor for locomotives gaining speed to ascend the eastern slope of the Sierra Nevada) and above the eastern marshes. It also was a suitable site for the junction with the proposed Virginia & Truckee Railroad (V&T), joining the Central Pacific with the booming Comstock Lode.

Lake deeded Central Pacific Railroad founder Charles Crocker forty acres of land to build the railway near his crossing. In exchange, Crocker agreed to build the depot in what was anticipated to be the center of town--a junction originally known as Argenta, but soon renamed Reno after Union Army General Jesse L. Reno. Connection to the completed V&T Railroad followed in 1872. Within a few decades, the Nevada-California-Oregon Railroad was established, connecting Reno to points north, and from 1904 to 1927, several streetcar lines also criss-crossed the town.