The name was derived from two words in the Nez Perce language to evoke the sense of "the place of pine trees and sestle."

The tribe found shade under the white pine trees for doing their work and stones suitable for use in pulverizing camas roots to process as one of their food staples.

The county comprises the majority of the eastern portion of the Palouse, famous for its rolling hills and rich agriculture.

The railroad's arrival in Moscow in 1885 led to its development as the primary population center of the county.

[17] Julieatta, Kendrick, and Troy were established as towns by the 1900 Census, with each incorporating as a village prior to 1910.

Lah-Toh contained all of northern Idaho west of Shoshone County between the Clearwater River and 48° north latitude.

Initially, the Governor granted the request, but later informed the residents that they were actually located within the boundary of Nez Perce County.

[25] The Idaho Territorial Legislature failed to address creation of a county for the residents of Moscow.

As a result, Fred T. Dubois successfully petitioned on their behalf for the United States Congress to create the county.

[26][27] In the 2022 University of Idaho killings, in the early morning hours of November 13, 2022, a mass murder took place in Moscow, in which four University of Idaho students were stabbed to death in an off-campus rented home by one or more attackers using one or more long knives.

[28][29] The Latah County coroner conducted autopsies on the four and said the victims all appeared to have been stabbed multiple times with a large knife, likely by the same weapon, that at least one (with apparently defensive stab wounds on her hands) and possibly more appear to have tried to fight off their attacker, and that they may have been attacked while sleeping in their beds.

The county ranks ninth for total number of registered voters and fifth within the 1st Congressional District.

[49] Similar to statewide results, Senator Ted Cruz of Texas carried Latah County in the Republican primary of 2016, and Donald Trump trailed by 1,208 votes.

[50] Senator Bernie Sanders of Vermont won the Democratic county caucus with 84% of the vote.

County residents voted Republican in the 2000 and 2004 presidential elections, but at a lower rate than the rest of the state.

George W. Bush carried Latah County in 2000 with 53.3% of the vote, but fell to 49.5% in 2004 as the Democratic share increased from 37.0% to 48.0%.

Barack Obama carried the county 51.9% to 45.1% in 2008 over John McCain, and won 49.6% to 45.3% in 2012 over Mitt Romney.

[51] On the precinct level, Democrats generally carry the university city of Moscow by moderate margins, and the rural remainder of the county is strongly Republican.