Born in Fauquier County, Virginia in 1758, Charles Lee was linked to an emerging political dynasty; relatives included brothers Henry Lee and Richard Bland Lee, and first cousin-once removed (as well as son-in-law) Richard Henry Lee. He was also third cousin of Zachary Taylor and grand-uncle of Fitzhugh Lee.

Charles Lee earned a bachelor of arts degree from the College of New Jersey (now Princeton University). Lee spent his early adulthood engaged more in military affairs than in politics, serving as an American naval officer from 1777 to 1789. Lee's transition to a political career began with his service as collector of the port of Alexandria (1789-1793), the appointment a favor from President George Washington. Lee achieved more notable political experience in 1794 following his election to Virginia's General Assembly, where he served until 1795. That year, President Washington named him United States attorney general, in which capacity Lee remained until the end of President John Adams' administration in 1801.

Lee then served one year as a circuit court judge (1801-1802) before establishing his own law practice, which dominated the remainder of his professional life. Noteworthy clients included Associate Justice Samuel Chase and Vice President Aaron Burr. He died in Fauquier County on June 24, 1815.