[2] The county was officially organized on February 14, 1845, and was named for the Oregon Territory in the northwestern United States.

Among the major first ancestries reported in Oregon County were 29.7% American, 13.4% English, 13.1% Irish, and 13.0% German.

[15] Political control at the county level is currently divided between the Democratic and Republican parties.

Smith won a special election on Tuesday, June 4, 2013, to finish out the remaining term of U.S. Representative Jo Ann Emerson (R-Cape Girardeau).

Emerson announced her resignation a month after being reelected with over 70 percent of the vote in the district.

At the presidential level, Oregon County was solidly Democratic from its founding in 1845 through 1996; in 1960, Richard Nixon became the first Republican ever to carry the county, but, aside from Nixon's landslide over McGovern in 1972, it would not go Republican again until 2000, when it voted for George W.

Like most rural areas throughout Southeast Missouri, voters in Oregon County generally adhere to socially and culturally conservative principles.

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.

During the same election, voters in five other states also strongly approved increases in the minimum wage.

In the 2008 presidential primary, voters in Oregon County from both political parties supported candidates who finished in second place in the state at large and nationally.

Senator Hillary Clinton (D-New York) received more votes, a total of 989, than any candidate from either party in Oregon County during the 2008 presidential primary.