Nelson was sent to England to be educated and after attending a private school at Hackney, he entered Christ's College, Cambridge, in May 1758, to stay until Ladyday in 1761.
While yet on board the vessel returning from England he had been chosen by the voters of York County to represent them in the House of Burgesses, but he soon took his place among his fellow planters in His Majesty's Council of Virginia in 1764. He went to the Continental Congress in 1775, resigning as colonel of the 2nd Virginia Regiment.
In the Virginia convention of 1776 he introduced the resolutions drafted by Edmund Pendleton and advocated by Patrick Henry calling upon Congress to declare the colonies free and independent. These resolutions passed the Virginia convention on May 15 and were taken by Nelson to the Congress in Philadelphia. Thus Thomas Nelson, the embodiment of wealth and established position in Virginia, stood shoulder to shoulder with the then impecunious frontiersman Henry as they swung their followings into the path of independence. When the Declaration of Independence was adopted Nelson was one of the Virginia signers.
Ill health, however, forced him to give up service in the Congress and he returned to Virginia in the spring of 1777.
Appointed by the governor and council of Virginia brigadier-general and commander-in-chief of the forces in the commonwealth, he raised a company with large personal expenditure and marched to Philadelphia in 1778, but these troops were disbanded when Congress felt unable to support them.
In 1779 Nelson returned to Congress but was ill again after several months of service and returned to Virginia to serve for the remainder of the conflict in the rôle of financier, governor, and commander of the militia of his state.
In 1781 he was elected in succession to Jefferson governor of Virginia, the first conservative to hold that office. His powers were strengthened by the legislature to meet the military crisis, but he even exceeded these grants of authority in his virtual position as military dictator. In September with over three thousand Virginia militia he joined Washington in the siege of Yorktown. His aid brought expressions of gratitude from Washington and his selfless patriotism in offering his own mansion in the town as a target for the bullets of his fellow countrymen has become one of the lasting tales of the Revolution in Virginia. Again the burden of office proved too great a strain for his constitution and he was forced to resign from the governorship before the end of 1781.
With the victory of the American cause Nelson reaped the ruin of his personal fortune. He sacrificed his private means to pay his public debts, accumulated in security for Virginia's loan of 1780 and in fitting out and provisioning troops. This course with the other hazards of the Revolution left him a poor man with a wife and eleven children. He moved to a small estate, "Offley, " in Hanover County, and there spent in simple surroundings the last years of his life.
Asthma, the foe he had fought so long, brought his death early in 1789. He was buried in the old churchyard at Yorktown.
As the first stages of the Revolution passed in Virginia Nelson supported ardently the preparation for war, especially Patrick Henry's motion to arm Virginia in March 1775.
Although he was an ardent revolutionist, he was in no sense a radical and he keenly opposed the Virginia Act of Sequestration of British property in 1777 and is said to have declared that he would pay his debts like an honest man.
The none too kindly pen of John Adams described Nelson, when they met in Philadelphia, as "a fat man, like the late Colonel Lee of Marblehead. He is a speaker, and alert and lively for his weight".
In the year after his return from England, on July 29, 1762, Nelson married Lucy, daughter of Philip and Mary (Randolph) Grymes, who bore him eleven children, among them Hugh Nelson.