James Gettys McGready Ramsey was born on March 25, 1797 to Francis and Peggy (Alexander) Ramsey in Knoxville, Tennessee. He was educated at Ebenezer Academy in Knox County and at Washington College before studying medicine, first under Dr. Joseph Strong in 1817 and then at the University of Pennsylvania in 1819. He married Margaret Barton Crozier on March 1, 1821 and together they had eleven children, including Robert McGready, Margaret Jane (Dickson), William Wilberforce, Henrietta Rutledge (Lenoir), John Crozier, Arthur Crozier, Elizabeth Alexander (Breck), James Gettys McKnitt, Charlotte, Francis Alexander, and Sue (Alexander). He built a large home on the French Broad and Holston Rivers which he named Mecklenburg. This was lost during the war and regained afterward through a series of lawsuits.

In addition to practicing medicine, Ramsey was active in public service, railroads, banking, and historical endeavors. He was instrumental in creating the East Tennessee and Georgia Railroad, in organizing the East Tennessee Historical and Antiquarian Society, and in supporting local educational institutions. During the Civil War, he publicly supported states' rights and served as a treasury agent and field surgeon for the Confederacy. His family was forced out of East Tennessee during the war, moving through Georgia and the Carolinas before returning to Knoxville in the early 1870s. While in exile in North Carolina, he wrote his autobiography, which was edited and published in 1984. He published several books during his life, the most famous of these being The Annals of Tennessee to the End of the Eighteenth Century, which was published in 1853.

Ramsey continued to play an active role in the Knoxville community until his death on April 14, 1884.