He was a Democratic lawyer. He served in the U.S. Army during the War of 1812. He was a member of Tennessee House of Representatives from 1815 to 1816 and a U.S. Senator from Tennessee from 1818 to 1821 and again from 1821 to 1829. His apparent age of 28 at the time of his inauguration is notable; it contradicted the US Constitution's requirement that all Senators be over the age of 30. At the time, many people did not know their actual birth records; although it is not certain what occurred in this case. In any event, if challenged, he could have referred to previous under-aged Senators Armistead Mason or Henry Clay.

He was a close personal friend of Andrew Jackson; after Jackson became President he, along with Postmaster General, Amos Kendall, were the only members of the official Cabinet who were also a member of Jackson's informal circle of advisors often satirically called by Jackson detractors the "Kitchen Cabinet". (Apparently this group did, in fact, frequently meet in the White House kitchen.) He resigned his Senate seat in 1829 in order to take up appointment as Jackson's Secretary of War, a post in which he served from 1829 to 1831, when he resigned from the Cabinet over a scandal concerning his second wife, Peggy, that was known as the Petticoat Affair. He was later Governor of Florida Territory from 1834 to 1836 and United States Minister to Spain from 1836 to 1840.

Eaton, a Freemason, died in Washington, D.C. on November 17, 1856. He was buried at Oak Hill Cemetery, Washington, D.C.

Eaton County, Michigan is named in his honor.

Preceded by: George W. Campbell U.S. Senator (Tennessee) 1818-1829 Succeeded by: Felix Grundy Preceded by: Peter Buell Porter United States Secretary of War 1829-1831 Succeeded by: Lewis Cass Preceded by: William P. Duval Territorial Governor of Florida 1834-1836 Succeeded by: Richard K. Call