After establishing a law practice in Lexington, Clay served in the State Legislature and also taught at Transylvania University in Lexington. He was a senator from Kentucky during the turbulent 1830's and '40's, when the national struggled with issues which ultimately led to the Civil War.

Clay's friendships included several in Nicholas County. Visiting Thomas Metcalfe, tenth governor of Kentucky, at his home on what is now Highway 68, he exclaimed, "Tom, you have a veritable forest retreat here," and the name remains to this day. Another prominent Nicholas Countian, Thompson S. Parks, lived at Parks Hill on the Licking River and entertained Clay, as he went to and from Washington, D. C. One of Parks' descendents treasures a flo-blue dinner plate which, family history holds, was part of a set presented to Parks by Clay. Clay is also remembered for his gift of gingko trees for county friends. One still stands on property at the corner of Locust and North Street in Carlisle.