West Hughes Humphreys began his career in law after passing the bar in 1828, establishing a private practice in Clarksville and later Somerville, Tennessee. He served in the Tennessee House of Representatives and as the 3rd Attorney General of Tennessee, where he also reported for the Tennessee Supreme Court. Humphreys transitioned to federal judicial service, confirmed by the Senate to a joint seat on the United States District Court for the Eastern, Middle, and Western Districts of Tennessee. His service ended due to impeachment and removal for supporting the Confederacy during the Civil War. Post-impeachment, he resumed private practice in Nashville until his death.

West Hughes Humphreys's political identity is marked by a complex blend of judicial service and controversial allegiances. His judicial career, which ended abruptly due to Confederate support, juxtaposes with his later advocacy for alcohol prohibition, suggesting a nuanced approach to moral governance. Humphreys's familial ties to the Ku Klux Klan through his daughter’s marriage add another layer of intrigue to his ideological positioning. This combination of roles and affiliations prompts questions about how he reconciles his judicial principles with his personal and familial connections to controversial movements.