John Church Hamilton trained in law after graduating from Columbia College in 1809 and served briefly in the War of 1812. Commissioned a second lieutenant, he worked as an aide to William Henry Harrison before resigning in 1814. His later career centered on historical research and his father Alexander Hamilton's papers. He worked with the family's collections and sought documents held by other participants in the founding era.

His research produced an early two-volume Life of Alexander Hamilton, issued in the 1830s and 1840. He collected and transcribed correspondence, arranged his father's writings, and pursued missing evidence; an 1838 letter, for example, requested Rufus King's notes from the Constitutional Convention. In 1850–1851 he published the seven-volume Works of Alexander Hamilton under congressional authorization, bringing together political, military, and official writings as well as correspondence.

Hamilton then recast and greatly expanded the biography as a history of the early republic, published in seven volumes from 1857 to 1864. The work defended his father's contribution to national government through a broad documentary narrative. His manuscripts and transcripts later entered Columbia's collections. Some copies preserve letters whose originals have since disappeared, giving his editorial work continuing research value beyond the family account. He remained associated with the preservation and commemoration of Alexander Hamilton until late in life.