In February 1807, while Bates was in Washington, President Thomas Jefferson appointed him to be Secretary of the Louisiana Territory, as well as a recorder of land titles.

Bates helped determine whether conflicting French, Spanish, and American land claims in the territory would be upheld, as it had been subject to three differing political systems.

[5] Jefferson had already decided on the returning explorer and fellow Virginian Meriwether Lewis as governor of the huge new Louisiana Territory, which approximately equaled the size of the existing United States.

He died in office in August 1825 in Chesterfield, Missouri, due to a short illness thought to be pneumonia.

In 1819, Bates married Nancy Opie Ball (1802–1877), daughter of a wealthy Virginia colonel.

The couple had four children, Emily Caroline (1820–1891), Lucius Lee (1821–1898), Woodville (1823–1840) and Frederick Jr.