Edward Hand trained in medicine and served with the British army before joining the American cause. He came to North America as a surgeon's mate with the 18th Royal Irish Regiment, serving at Fort Pitt. Resigning in 1774, he settled in Lancaster, Pennsylvania, to practice medicine. In 1775 he joined the Continental Army as lieutenant colonel of Pennsylvania riflemen and subsequently became a colonel. His early campaigns included the siege of Boston and the fighting around New York and Trenton.

Promoted to brigadier general in 1777, Hand commanded at Fort Pitt, dealing with frontier warfare and efforts to organize militia. His expedition in 1778 attacked a neutral Lenape community and killed people who were not the intended British-allied enemy. In 1779 he commanded the light troops of the Sullivan expedition against Haudenosaunee settlements in New York, a campaign that destroyed villages and food supplies. These operations formed a destructive part of the struggle for control of Indigenous homelands.

In 1781 Hand became adjutant general of the Continental Army, overseeing staff business and serving during the Yorktown campaign. He remained in service until 1783, receiving brevet promotion to major general before resigning. Returning to Lancaster, he resumed civilian responsibilities and developed the Rock Ford estate, where his family moved in 1794. His surviving correspondence documents both military affairs and household concerns. He died in 1802.