James Knox Polk was born November 2, 1795–the first of ten children born to Samuel and Jane Knox Polk. The Polk family, originally from Ireland, had moved a generation before to rural Mecklenburg County, North Carolina, from their old home in Pennsylvania. Although farmers by trade, the Polk family had always been a family of leaders. Mecklenburg, a mostly agrarian community, was now led by Thomas Polk, James's great-uncle. And James's maternal grandfather, James Knox, had already distinguished himself fighting in the Revolutionary War.

Polk, however, did not appear to be fit for a life of greatness. He certainly was not fit for a life on the frontier of America. Although he hunted and fished and loved to ride horses, Polk remained a sickly child. He was underweight for much of his childhood, and enjoyed little of his daily chores on the farm. His mother taught him to read and write by the fire at night while his grandfather and father traded stories of the war and discussed Federalist politics. The family had developed strong opinions during the adoption of the Constitution in the 1780s and now spent long hours debating the merits of Federalism and Jeffersonian democracy.

In the fall of 1806, the Polk family moved to Tennessee. Ironically, Polk and his new home state were the same age–Polk had been born just seven months after Tennessee joined the Union. Around the fall of 1809, Polk's sickliness began to worry his parents and they sent him to a doctor in Kentucky, over two hundred miles away. There, the doctor diagnosed him with gallstones and operated on the young boy. Operations in those days, however, offered little in the way of anesthetics (other than brandy) and Polk recalled the surgery as a terrible ordeal. On the other hand, it did offer Polk a chance to demonstrate his courage and fortitude. After his operation, he knew he cold handle just about anything. Despite the successful removal of his gallstones, he never regained all of his strength and as weeks dragged into months and Polk still lacked the vigor to farm, his father apprenticed him to a Columbia storekeeper. Polk soon discovered that of the few things he disliked more than farming, shopkeeping was high on the list. He lasted but a few weeks before he returned to the farm. He decided to enter a more intellectual profession, like law. His mother hoped he would enter the ministry, but Polk had other ideas.

And so, at the age of seventeen, Polk's formal education began. Dr. Robert Henderson tutored the young man in the classics, literature and the ministry, but Polk had little interest in divinity school. Polk excelled at his lessons. He had finally found something that interested him and something at which he was good. A year later, he entered a private school in Mulfreesboro, fifty miles from his hometown. His father cautioned that he would pay for college if Polk studied, but that he wouldn't waste his money if Polk failed. The warning was unnecessary, however. Polk threw himself into the academy like nothing he had yet done. He sharpened his wit and devoured any book he could find.

After only a year at the private school, he entered the University of North Carolina as a sophomore. Over the next three years, his determination and studiousness would became legendary and would propel him to the head of the class by his graduation with the Class of 1818. He graduated as class salutatorian with Highest Honors in math and the Classics.

Upon graduation, Polk began a one-year study of law with Felix Grundy in Nashville, before opening his own office (with a whitewashed sign reading "J.K. Polk, Attorney-at-Law") next to the office of Aaron V. Brown, his best friend from college. His father offered to help him with money during his first year, but Polk soon found himself to be quite successful as a lawyer and within three years he found himself making a "fabulous" amount of money. His father, too, had succeeded and had moved the family to a brick mansion on the best street in Columbia. The family's prospects looked good.