Republicans hold one of the three U.S. Congressional seats (VA-1) that include parts of Prince William County. In 2006, Democratic U.S. Senator candidate Jim Webb carried the county with 50.51% of the vote.

In the 2008 United States presidential election, Democrat Barack Obama carried Prince William with 57.51% of the vote, compared to Republican John McCain who received 41.62%. Obama's final rally the night before the election was held at the Prince William County Fairgrounds, just outside the city of Manassas. He was the first Democrat to carry the county since 1964.

Continuing demographic changes in the county, such as an increasingly diverse and urbanized population, were cited by The New York Times as contributing to Obama's success in the 2012 United States presidential election and suggesting the future appeal of the Democratic Party in the United States. Between 2000 and 2010, county population had increased by 121,189 persons (43.2%). It had changed from a primarily white, rural county. Prince William by 2012 had an educated professional population with the seventh-highest income in the country; it is the first county in Virginia to be composed of a majority of minorities: Hispanic, African American, and Asian. Obama and the Democrats attracted their votes.[13] Time identified Prince William as one of five critical counties in Virginia for the election. Obama defeated Romney soundly by 16 percentage points with a margin of 57%–41%,[21] narrowly beating his 2008 margin.

The county continued its trend toward Democratic candidates in the 2016 United States presidential election, Prince William County voted 57.6% for Hillary Clinton to Trump's 36.5%. Clinton's victory represented the largest margin of victory for any presidential candidate in the county since 1988. In 2020, Prince William County voted for Joe Biden with 62.6% of the vote, the largest share of the vote for a Democratic candidate since 1944.