In 1866, the Union Pacific Railroad reached present-day Schuyler, at the time known as Shell Creek Station. Three years later, the Nebraska State Legislature divided large Platte County into three smaller counties, including Colfax county. In 1870, Shell Creek Station was renamed Schuyler, after Schuyler Colfax--the U.S. Vice President under Ulysses S. Grant. 

In 1870, the Union Pacific chose the town as the point at which Texas cattle being driven north would be loaded onto trains--making Schuyler the first "cow town." However, the resulting boom, which saw a six-fold increase in the town's population (100 growing to 600) and around 50,000 head of cattle pass through, was only temporary as the cattle trail had moved west to Kearney by the following year. 

The city's early residents were Czech, Irish, and German settlers. The settlement was enabled by Schuyler's geographic position, which caused the community to be associated with a number of historic overland transportation routes including the Oregon Trail, the Morman Trail, the Transcontinental Railway, and the Lincoln Highway. 

Beginning in the late 1980s, reductions in wages at the Cargill plant led to a change in Schuyler's demographic makeup. By 2017, an estimated 60% of the population was Latino, and immigrants from other parts of the world, including Somalia and Thailand, had also moved into the city.