The county is located at the northern end of the Front Range, at the edge of the Colorado Eastern Plains along the border with Wyoming.

The river itself received its name in the middle 1830s from an obscure incident in which French-speaking trappers hid gunpowder along its banks, somewhere near present-day Laporte or Bellvue.

Janis, who had visited the area near Bellvue in 1844 and proclaimed it "the most beautiful place on earth", returned to file his official claim and helped found the first U.S. settlement in present-day Colorado, called Colona, just west of Laporte.

Nearly simultaneously, Mariano Medina established Fort Namaqua along the Big Thompson River just west of present-day Loveland.

By that time, Mason and others had convinced the Colorado Territorial Legislature to designate the new town as the county seat.

Along the new railroad sprung up the new platted towns of Loveland and Berthoud, named respectively after the president and chief surveyor of the Colorado Central.

Although the line was never extended over the mountains, it opened up the quarrying of stone for the railroad at Stout, furnishing another industry for the region.

The brief attempt at the mining of gold in the region centered at the now ghost town of Manhattan in the Poudre Canyon.

The early growth of agriculture, which depended highly on direct river irrigation, experienced a second boom in 1902 with the introduction of the cultivation of sugar beets, accompanied by the construction of the large processing plant of the Great Western Sugar Co. in Loveland.

In the following decade, the sugar beet industry brought large numbers of German emigrants from the Russian Empire to the county.

This project collected and captured Western Slope water, and carried it over to the Front Range Colorado counties of Boulder, Larimer, and Weld, along with extensive water storage and distribution system, which significantly extended the irrigable growing season and brought substantial additional land under irrigation for the first time.

However, increasing urbanization, as well as the influence of Colorado State University, caused the Republican margins to decline steadily in the 1990s and early 2000s.

In 2020, Joe Biden's margin of victory was even greater and in 2024, Larimer was one of the few counties nationwide to swing towards Kamala Harris.