Born in Culpeper County, Virginia, Walker attended the common schools and served in the American Revolutionary War.
He was admitted to the bar and commenced practice in Nicholasville, Kentucky, in 1799.
He was then appointed to the United States Senate to fill the vacancy caused by the resignation of George M. Bibb, and served from August 30, 1814, to February 2, 1815, when a successor was elected.
He was also the uncle of two governors of Florida, Richard Keith Call and David Shelby Walker.
Another nephew John George Walker served as a general in the Confederate Army during the Civil War.