Historically, Napa County was heavily Republican. It only supported a Democrat for president seven times – four of which were for Franklin D. Roosevelt – in the thirty-two presidential elections between 1860 and 1988. However, a Republican hasn't carried the county since George H. W. Bush in 1988. It is now one of the most Democratic counties in California, and is reckoned as part of the solid bloc of blue counties in the northern part of the state.

On November 4, 2008, Napa County voted 56 percent against Proposition 8, which amended the California Constitution to ban same-sex marriages.

According to the California Secretary of State, as of February 10, 2017, Napa County has 76,038 registered voters, out of 93,926 eligible (81.0%). Of those, 35,660 (46.9%) are registered Democrats, 18,417 (24.2%) are registered Republicans, and 17,827 (23.4%) have declined to state a political party.