Lieutenant governor of the Province of Pennsylvania
Hamilton became a member of the provincial council in 1746. He was commissioned by the sons of William Penn to serve as lieutenant governor of the Province of Pennsylvania, serving in that capacity until 1754, then again from 1759 to 1763, and briefly in 1771 and 1773.
On September 13, 1761, Hamilton and William Allen conveyed Lot no. 1 and the other pieces of property obtained by Andrew Hamilton and Allen to Isaac Norris II and the other trustees in charge of purchasing property for the Philadelphia State House, which was later renamed Independence Hall. The conveyance of this land completed the area of the yard: property that contained the state house and the public spaces surrounding it.
During the period when Philadelphia was the federal capital of the United States, prior to its relocation to Washington, D.C., in 1800, Hamilton was on an extended stay in England. He rented Bush Hill to the federal government for residential use by the vice president.
Hamilton was visiting London in 1748, when he received the commission of deputy governor for the province from the Penns. Upon his return to Philadelphia, Hamilton faced unrest from the Native American population. Their territory north of the Blue Mountain, west of the Susquehanna River, was being encroached upon by settlers illegally. Hamilton authorized Richard Peters and Conrad Weiser to assist in removing these squatters after the provision in the Land Purchase of 1749, which authorized their removal by force if necessary.
Other issues Hamilton confronted included:
Encroachment of the French Military into forts in the land of the Pennsylvania Charter at Presque Isle, Venango, La Boeuf and Du Quesne.
Organizing and funding a defense against the French in opposition to the pacifist Quaker element in the Assembly
Friction between the Assembly and Proprietors on taxing Proprietary land holdings
Assembly discontent over the Proprietors' refusal to hear appeals from them about the Deputy Governor's decisions
Failure to disclose to the Assembly, the Proprietors' directive concerning the financial interest of pecuniary bills which Hamilton would approve
Albany Congress attended by John Penn and Benjamin Franklin, who proposed a colonial union for defense against the French and Indians
Hamilton resigned due to his deteriorating relations with the Assembly in the attempt to follow the proprietors' instructions.
Hamilton's second turn as deputy governor followed the recall of William Denny. The French and Indian War was coming to its conclusion. However, the Province of Pennsylvania was then facing Pontiac's War. The Lenape and Shawnee tribes raided deep into frontier Pennsylvania, taking captives and killing settlers. An uprising led by a vigilante group, known as the Paxton Boys, erupted in Province of Pennsylvania. Hamilton was replaced by John Penn, William Penn's grandson.