Atchison was a member of the Democratic Party and played a significant role in the politics of the pre-Civil War era. One notable aspect of Atchison's political career is the controversy surrounding his alleged presidency for one day. According to a popular myth, Atchison served as the President of the United States on March 4, 1849. The story goes that President-elect James K. Polk's term ended on a Sunday, and as Zachary Taylor refused to be inaugurated on a Sunday, Atchison, as the President pro tempore of the Senate, became the acting president for a day. However, this claim is not supported by historical evidence, and Atchison himself denied it. In terms of his political positions, Atchison was known for his strong support of slavery and states' rights. He played a significant role in the debates over the expansion of slavery into new territories, particularly during the Kansas-Nebraska Act of 1854. Atchison strongly advocated for allowing settlers in these territories to decide whether to permit slavery or not, a principle known as popular sovereignty.

During his time in the Senate, Atchison also held various leadership positions. He served as the President pro tempore of the Senate from 1846 to 1849 and again from 1852 to 1854. This position made him third in line to the presidency at the time. After leaving the Senate in 1855, Atchison continued to be involved in politics but did not hold any significant public office. He supported the Confederacy during the American Civil War and served as a Confederate general in the Missouri State Guard. David Rice Atchison died on January 26, 1886, in Gower, Missouri. Despite the myth surrounding his one-day presidency, he is primarily remembered for his staunch support of slavery and his role in the debates leading up to the Civil War.