He marched with the regiment to Fort Pitt, on the forks of the Ohio River, returning to Philadelphia in 1774, where he resigned his commission.

Promoted to brigadier general in March 1777, he served as the commander of Fort Pitt, fighting British loyalists and their Indian allies.

However, failing to distinguish among Native American groups, the unruly militiamen under Hand's command attacked the neutral Lenape village of Kuskusky, killing the mother, brother, and a child of Chief Hopocan, known as Captain Pipe.

[4] Hand was later recalled after serving over a year at Fort Pitt (June 1777 to August 1778),[5] to command a brigade in Major General La Fayette's division.

In the resulting Sullivan-Clinton Iroquois Expedition (May-November 1779) through the Southern Tier and Finger Lakes regions of New York, Edward Hand commanded the Third Brigade, composed of the Fourth and Eleventh Pennsylvania Regiments, the German Regiment, Proctor’s Artillery, Captain James Parr’s Riflemen, Captain Anthony Selin’s Riflemen, and two Wyoming companies.

[5] After a few months, he was appointed Adjutant General of the Continental Army and served during the siege of Yorktown in that capacity.

A Federalist, Hand was active in civil affairs, holding posts that included: Beginning in 1785, he owned and operated Rock Ford plantation, a 177-acre (0.72 km2) farm on the banks of the Conestoga River, one mile (1.6 km) south of Lancaster, Pennsylvania.

The Georgian brick mansion remains today; the farm is a historic site open to the public.