Born and raised in Boston, he owned and operated a bookstore there, cultivating an interest in military history and joining a local artillery company. On March 5, 1770 Knox was a witness to the Boston Massacre, and according to eyewitness accounts, he attempted to defuse the situation by trying to convince the British soldiers to return to their quarters.
It is unknown if Knox participated in the 1773
Boston Tea Party, but he did serve on guard duty before the incident to make sure no tea was unloaded from the Dartmouth
When the war broke out in 1775, he befriended General George Washington, and quickly rose to become the chief artillery officer of the Continental Army. Knox is credited with breaking the stalemate during the Siege of Boston when he seized cannon from Fort Ticonderoga in upstate New York and commenced what came to be known as the “Noble train of artillery”. This “train” of men and beasts hauled 60-tons of cannon and armaments across 300 miles of ice and snow- by ox-driven sled- up and over the Berkshire Mountains and eventually into Boston.