On Tuesday night, as most of the country turned red, rock-solid-red Orange County, Calif., went blue.

Southern California’s cradle of conservatism voted for Hillary Clinton, the first time the county supported a Democratic presidential candidate since it helped to elect Franklin Delano Roosevelt in 1936.

The historic flip is a powerful signal of California’s new rebel status. The nation’s most populous state, which has been in virtual lockstep with policies of the Obama White House, now stands again as the country’s political outlier.

Ms. Clinton won 62% of the California vote, according to an initial tally by the Associated Press.

“We woke up feeling like strangers in a foreign land,” California Senate President pro Tempore Kevin de León and Assembly Speaker Anthony Rendon—both Latinos—said in a statement, and pledged to preserve the state’s liberal policies.