It is named after Ensign Sieur Jean Baptiste de Girardot (also spelled Girardeau or Girardat), a French officer stationed 1704–1720 at Kaskaskia in the Illinois Country of New France.

In the second verse, the singer refers to having "been all around Cape Girardeau and parts of Arkansas...poor boy, I've been all around this world."

The most predominant denominations among residents in Cape Girardeau County who adhere to a religion are Roman Catholics (19.19%), Assemblies of God (19.13%), and Lutherans (LCMS) (16.58%).

Of adults 25 years of age and older in Cape Girardeau County, 81.1% possess a high school diploma or higher while 24.2% hold a bachelor's degree as their highest educational attainment.

Cape Girardeau County, along with the rest of the state of Missouri, is represented in the U.S. Senate by Josh Hawley (R-Columbia) and Roy Blunt (R-Strafford).

In contrast, much of southern Missouri was solidly Democratic for much of the 20th century before swinging heavily Republican at the turn of the millennium.

Since 1888, it has voted Democratic only in Franklin Roosevelt's and Lyndon Johnson's 40-state landslides of 1932, 1936, and 1964; in the three-way race in 1912 (when it gave Woodrow Wilson a plurality); and for Missouri native Harry Truman in 1948.

[17] Like most areas throughout rural Missouri, voters in Cape Girardeau County generally adhere to socially and culturally conservative principles which have influenced their shift to Republicans.

In 2006, Cape Girardeau County voted against a state constitutional amendment to fund and legalize embryonic stem cell research, with 63.12 percent opposed.

On the Democratic side, former Vice President Joe Biden (D-Delaware) both won statewide and carried Cape Girardeau County by a wide margin.

Incumbent President Donald Trump (R-Florida) faced a primary challenge from former Massachusetts Governor Bill Weld, but won both Cape Girardeau County and statewide by overwhelming margins.

Businessman Donald Trump (R-New York) narrowly won the state overall, but Senator Ted Cruz (R-Texas) carried a plurality of the vote in Cape Girardeau County.

On the Democratic side, former Secretary of State Hillary Clinton (D-New York) narrowly won statewide, but Senator Bernie Sanders (I-Vermont) carried a majority of the vote in Cape Girardeau County.

Senator Rick Santorum (R-Pennsylvania), who finished first in the state at large, but eventually lost the nomination to former Governor Mitt Romney (R-Massachusetts).

In 2008, the Missouri Republican Presidential Primary was closely contested, with Senator John McCain (R-Arizona) prevailing and eventually winning the nomination.

Then-Senator Hillary Clinton (D-New York) received more votes than any candidate from either party in Cape Girardeau County during the 2008 presidential primary.

Despite initial reports that Clinton had won Missouri, Barack Obama (D-Illinois), also a Senator at the time, narrowly defeated her statewide and later became that year's Democratic nominee, going on to win the presidency.