Nathanael Greene was born August 7, 1742 and the son of Nathanael Greene, a Quaker farmer, and his wife Mary Motte (father’s second wife). The Greenes lived in Warwick, Rhode Island. Greene educated himself in the study of mathematics and law. In 1770, Greene moved to Coventry, Rhode Island, to take charge of the family-owned foundry, just prior to his father's death. Having been self taught he was one of the first to urge the establishment of a public school.

In 1774 Greene married Catherine (Caty) Littlefield of Rhode Island and they had six children. That same year, he helped organize a local militia known as the Kentish Guards that October. Greene was confronted by some members because he had a severe limp. It was during this time that Greene began to study volumes on military tactics and to teach himself the art of war. In December 1774, he was on a committee appointed by the state general assembly to revise the militia laws. His passion in fighting the British and organizing the militia led to his expulsion from the pacifistic Quakers.

By May 1775, he had been promoted from private to Major General of the Rhode Island Army of Observation formed in response to the Siege of Boston. He was appointed a brigadier of the Continental Army by the Continental Congress in June 17755. General George Washington assigned Greene the command of the city of Boston after it was evacuated by the British in March 1776. On August 9, 1776, Greene was appointed one of four new major generals and was placed in command of the Continental army troops on Long Island. It was he who chose the place for fortifications, and supervised the construction (the site today is Fort Greene Park) east of Brooklyn Heights.

Greene was ill  during the Battle of Long Island and did not participate. At the Battle of Trenton, Greene commanded one of two American columns. He was in command of Fort Lee in New Jersey. On October 25, 1776, he was placed in command of  Fort Washington, across the river from Fort Lee. He received orders from General Washington to defend Fort Washington at all cost. Even thought the blame for the losses of Forts Washington and Lee was put upon Greene, he did not lose the confidence of Washington. Greene commanded the reserve at the Battle of Brandywine. At Germantown Greene's command arrived in time to support efforts there and Greene and his troops distinguished themselves.

On March 2, 1778, at Valley Forge, General Washington requested Greene accept the office of Quartermaster General. Greene accepted on the condition that he retain the right to command troops in the field. This led to him heading the right wing at Monmouth June 28, 1778. Greene and Lafayette commanded the land forces sent to Rhode Island to co-operate with the French admiral d’Estaing in an expedition (the Battle of Rhode Island) which proved unsuccessful. In June 1780, Greene was in command at the Battle of Springfield. Later he resigned the office of Quartermaster General, citing Congress’s interference in certain areas of suppling the Continental army.

On October 5 General Washington appointed Greene to replace Major General Gates in the South. Congress approved the appointment and Greene was given command over all troops from Delaware to Georgia. Greene took command at Charlotte, North Carolina on December 2, with Brig. General Isaac Huger of the South Carolina Continentals being his second in command. Greene’s army was weak, badly equipped, and opposed by a superior British force. Greene decided to divide his own troops, and this led to success at the Battle of Kings Mountain in 1780 under Colonel William Campbell. General Daniel Morgan was victorious at Cowpens on January 17, 1781. After other encounters, Greene would write "In all probability you will find me on the North side of Dan River. I must repeat it, the present moment is big with the most important consequences, & requires the greatest & most spirited exertions."

In February 1781, Greene and the Southern American army would be involved in the race to and the crossing of the Dan River in Halifax County, Virginia. This would be considered a major event in the South, one that lead to the surrender later at Yorktown. According to Dennis M. Conrad, Project Director and Editor, The Papers of General Nathanael Greene, this “American retreat, which extended across the breadth of North Carolina, is considered one of the masterful military achievements of all time."

Greene was an original member of the Rhode Island Society of the Cincinnati and served as the Society's president from its founding in 1783 until his death. He died on June 19, 1786, and was buried in the cemetery of Christ Episcopal Church in Savannah.  In 1902 his remains were reinterred beneath the Greene monument erected in Johnston Square in Savannah. North Carolina, South Carolina, and Georgia voted Greene liberal grants of lands and money, including an estate, “Boone's Barony,” south of Edisto in Bambery County. He sold most of the estate to pay bills for the rations of his Southern army. After twice refusing the post of Secretary of War, Greene in 1785, settled on his Georgia estate Mulberry Grove. He died at 43 years old on the estate on June 19, 1786, of a sunstroke. Greene was a self-trained soldier, ranked high in military ability, and served during the entire American Revolution.