Born near Harrodsburg, Kentucky, Thompson grew up in a pro-slavery household with parents who owned six slaves.

In 1840, he was elected as a Whig to the United States House of Representatives to fill the vacancy in Kentucky's 5th District caused by the death of Simeon H. Anderson.

He had been a Clay Whig until the disruption of the party just before the US Civil War, when he became a Constitutional Unionist.

[6] On September 24, 1857, the Springfield Daily Republican published an article titled "Bogus Fugitives".

George said that he was the slave of Senator Thompson of Kentucky and that he had been his body servant in Washington.

The article is written to dissuade the public from believing this information and claims that George Thompson "is said to be very shrewd and adept at humbug.

"[7] In early February 1859, the Cleveland Herald published an article titled "What a Batch of Pies Cost a United States Senator."

On March 28, 1868, he married Mary Hardin (Chinn) Bowman in Harrodsberg, Mercer County, Kentucky.

[citation needed] Thompson died in Harrodsburg and was interred in Spring Hill Cemetery.