Davie's law studies in Salisbury, NC, were interrupted by military service, but he won his license to practice before county courts in 1779 and in the superior courts in 1780. When the War for Independence broke out, he helped raise a troop of cavalry near Salisbury and eventually achieved the rank of colonel. While attached to Pulaski's division, Davie was wounded leading a charge at Stono, near Charleston, on June 20, 1779. Early in 1780 he raised another troop and operated mainly in western North Carolina. In January 1781 Davie was appointed commissary-general for the Carolina campaign. In this capacity he oversaw the collection of arms and supplies to Gen. Nathanael Greene's army and the state militia.

After the war, Davie embarked on his career as a lawyer, traveling the circuit in North Carolina. In 1782 he married Sarah Jones, the daughter of his former commander, Gen. Allen Jones, and settled in Halifax. His legal knowledge and ability won him great respect, and his presentation of arguments was admired. Between 1786 and 1798 Davie represented Halifax in the North Carolina legislature. There he was the principal agent behind that body's actions to revise and codify state laws, send representatives to the Annapolis and Philadelphia conventions, cede Tennessee to the Union, and fix disputed state boundaries.

During the Constitutional Convention Davie favored plans for a strong central government. He was a member of the committee that considered the question of representation in Congress and swung the North Carolina delegation's vote in favor of the Great Compromise. He favored election of senators and presidential electors by the legislature and insisted on counting slaves in determining representation. Though he left the convention on August 13, before its adjournment, Davie fought hard for the Constitution's ratification and took a prominent part in the North Carolina convention.

The political and military realms were not the only ones in which Davie left his mark. The University of North Carolina, of which he was the chief founder, stands as an enduring reminder of Davie's interest in education. Davie selected the location, instructors, and a curriculum that included the literary and social sciences as well as mathematics and classics. In 1810 the trustees conferred upon him the title of "Father of the University" and in the next year granted him the degree of Doctor of Laws.

Davie became Governor of North Carolina in 1798. His career also turned back briefly to the military when President John Adams appointed him a brigadier general in the U.S. Army that same year. Davie later served as a peace commissioner to France in 1799.

Davie stood as a candidate for Congress in 1803 but met defeat. In 1805, after the death of his wife, Davie retired from politics to his plantation, "Tivoli," in Chester County, South Carolina. In 1813 he declined an appointment as major-general from President Madison. Davie was 64 years old when he died on November 29, 1820, at "Tivoli," and he was buried in the Old Waxhaw Presbyterian Churchyard in northern Lancaster County.