Amherst received a commission in the foot guards in 1731 and was selected as aide-de-camp first by Lord Ligonier and then by the duke of Cumberland. William Pitt and Ligonier selected him for the Canadian command in 1758. With a force of 14,000 men, he besieged and captured Louisbourg (on Cape Breton Island) and was promoted to chief command in America. He then drew up a plan for a concentric advance on Montreal by three columns, one moving westward up the St. Lawrence River and capturing Quebec, the second northward from Albany by Ticonderoga and Crown Point, and the third eastward from Fort Niagara. The first column, under the command of James Wolfe (Wolfe, James), captured Quebec in 1759, and the final offensive was launched in 1760, when Montreal surrendered and Canada passed into British hands.

Amherst remained in North America as commander in chief until 1763, quelling the Indian rising under Pontiac in 1761. Before his retirement in 1796, he acted as commander in chief of the British army on two occasions, successfully suppressing the Gordon riots in 1780. Notably, he refused to take part in the war with the American colonies (the American Revolution).

He was created a baron in 1776 and a field marshal in 1796.