Charles Willing Byrd began legal work in the 1790s and served as a land agent for the financier Robert Morris at Lexington, Kentucky, from 1794 to 1797. He then practiced law in Philadelphia. President John Adams appointed him secretary of the Northwest Territory in 1799, and he took the oath in 1800. The office brought him into the disputes over territorial government and the movement to create a state from its eastern portion.

Byrd represented Hamilton County at Ohio's constitutional convention in 1802. After Arthur St Clair's removal, he acted as territorial governor during the transition to statehood. His executive authority ended as Ohio's new government took office in 1803. Thomas Jefferson nominated him to the newly created United States District Court for Ohio on March 1, 1803; Senate confirmation and his commission followed two days later. He became the state's first federal district judge.

He remained on the bench until his death in 1828. The court's business included disputes arising from western settlement, federal law and the relationship between state and national authority. It became involved in proceedings connected with Aaron Burr's western expedition and in the controversy over Ohio's attempt to tax branches of the Bank of the United States. Alongside judicial work, Byrd acquired property and lived at several locations in southern Ohio, eventually settling at Sinking Spring. He served through Ohio's territorial transition and early federal judiciary.