The French explorers Renault and La Motte entered the area of present-day Potosi in 1722–23. However, no permanent settlements were made until 1763, when François Breton settled near Potosi and began to operate a mine bearing his name. The Bellview Valley, near Caledonia and Belgrade, was settled in 1802 by the families of William and Helen Watson Reed, their sons, Robert, Joseph, and Thomas Reed, William Reed's brother and nephew, Joseph and William Reed, Annanias McCoy, and Benjamin Crow. Washington County was officially organized on August 21, 1813, out of Ste. Genevieve County.
As of the census of 2000, there were 23,344 people, 8,406 households, and 6,237 families residing in the county. The population density was 31 inhabitants per square mile (12/km2). There were 9,894 housing units at an average density of 13 per square mile (5/km2). The racial makeup of the county was 95.47% White, 2.48% Black or African American, 0.66% Native American, 0.15% Asian, 0.01% Pacific Islander, 0.15% from other races, and 1.08% from two or more races. Approximately 0.73% of the population were Hispanic or Latino of any race.
There were 8,406 households, out of which 36.40% had children under the age of 18 living with them, 58.60% were married couples living together, 10.60% had a female householder with no husband present, and 25.80% were non-families. 22.00% of all households were made up of individuals, and 9.40% had someone living alone who was 65 years of age or older. The average household size was 2.64 and the average family size was 3.05.
In the county, the population was spread out, with 26.60% under the age of 18, 9.80% from 18 to 24, 29.20% from 25 to 44, 22.70% from 45 to 64, and 11.70% who were 65 years of age or older. The median age was 35 years. For every 100 females there were 106.40 males. For every 100 females age 18 and over, there were 106.40 males.
The median income for a household in the county was $32,001, and the median income for a family was $38,193. Males had a median income of $27,871 versus $18,206 for females. The per capita income for the county was $16,095. About 17.10% of families and 20.80% of the population were below the poverty line, including 25.40% of those under age 18 and 12.90% of those age 65 or older.
At the presidential level, Washington County was a fairly independent-leaning or battleground county for many years, however, it has voted increasingly more Republican in recent elections. While George W. Bush carried Washington County in 2004, he narrowly lost the county to Al Gore in 2000, and both times the margins of victory were significantly closer than in many of the other rural areas. Bill Clinton also carried Washington County both times in 1992 and 1996 by convincing double-digit margins, and unlike most of the other rural counties in Missouri, Washington County was one of only nine counties in Missouri that favored Barack Obama over John McCain. Obama won Washington County by just five votes in the 2008 election.
Like most rural areas throughout Missouri, voters in Washington County generally adhere to socially and culturally conservative principles but are more moderate or populist on economic issues, typical of the Dixiecrat philosophy. In 2004, Missourians voted on a constitutional amendment to define marriage as the union between a man and a woman—it overwhelmingly passed Washington County with 81.37 percent of the vote. The initiative passed the state with 71 percent of support from voters as Missouri became the first state to ban same-sex marriage. In 2006, Missourians voted on a constitutional amendment to fund and legalize embryonic stem cell research in the state—it failed in Washington County with 56.48 percent voting against the measure. The initiative narrowly passed the state with 51 percent of support from voters as Missouri became one of the first states in the nation to approve embryonic stem cell research. Despite Washington County's longstanding tradition of supporting socially conservative platforms, voters in the county have a penchant for advancing populist causes like increasing the minimum wage. In 2006, Missourians voted on a proposition (Proposition B) to increase the minimum wage in the state to $6.50 an hour—it passed Washington County with 81.47 percent of the vote. The proposition strongly passed every single county in Missouri with 75.94 percent voting in favor as the minimum wage was increased to $6.50 an hour in the state. In 2018, Washington County rejected Proposition A which would have made Missouri a right to work state with 82.1 percent of the vote.
Donald Trump won the county with 75% of the vote in 2016, continuing a trend of white, rural Midwestern counties that had voted for Obama in 2008 and/or 2012 and had swung hard to Trump in 2016. The Trump campaign had made promises to bolster the jobs situations in the Rust Belt, which combined with elevated social liberalism from the Democrats, may have played a role in the margins—which could be said for various other white working-class Midwestern counties that did the same.
In the 2008 presidential primary, voters in Washington County from both political parties supported candidates who finished in second place in the state at large and nationally.
Former U.S. SenatorHillary Clinton (D-New York) received more votes, a total of 2,345, than any candidate from either party in Washington County during the 2008 presidential primary. She also received more votes, almost double, than the total number of votes cast in the entire Republican Primary in Washington County. Washington County was Clinton's fifth strongest county in Missouri; she only did better in Dunklin, Wayne, Carter and Ripley counties.