King's College established the second medical school in the Thirteen Colonies in 1767. The school awarded its first degree, a B.A. in medicine, in 1769 and the next year it became the first institution in the Colonies to confer the M.D.

Instruction ceased during the American Revolution, when King's College closed entirely. The College, renamed Columbia, reopened in 1784, but the medical faculty was not revived until Fall, 1791. It failed to thrive, graduating only 35 students between 1793 and 1813.

Efforts began as early as 1811 to merge Columbia's medical school into the more vigorous College of Physicians and Surgeons (P&S), which had been founded in 1807 with a charter from the New York State Board of Regents. An agreement by which P&S absorbed all of Columbia's students and faculty was reached by the end of 1813; the Board of Regents officially approved the merger in 1814. Though P&S forged a nominal alliance with Columbia in 1860, the medical school would not truly be integrated into Columbia until the full merger of 1891.