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Charles was the eldest son of Charles Cornwallis, 5th Baron Cornwallis, who was created 1st Earl Cornwallis in 1753. He was styled Viscount Brome from 1753 until he succeeded his father as 2nd Earl Cornwallis in 1762. Cornwallis was educated at Eton and Clare College, Cambridge, and then entered the army, rising to the rank of major-general by 1775.
When hostilities broke out in America in 1775, Cornwallis volunteered for service. He sailed for New York in February 1776 in charge of seven regiments. He commanded one wing at the battle of Long Island in August, and fought in New Jersey in the autumn and winter. In 1777 he attacked Philadelphia and was victorious at the battle of Brandywine.
In 1778 Cornwallis was promoted to lieutenant-general and second-in-command under Sir Henry Clinton. His ideas concerning the occupation of ports were not heeded by Clinton, and Cornwallis returned to England briefly, coming back to America in 1779. In May 1780 Clinton and Cornwallis took Charlestown, South Carolina. Cornwallis was left in charge in the south. The following year he decided to move north to Virginia to meet up with other British forces. He was ordered to remain at Yorktown, where he was exposed to a siege by a combined force led by George Washington and the French navy. Clinton was too late to relieve Cornwallis, who surrendered his army on 19 October 1781, marking the effective end of the American Revolutionary War.
In 1786, Cornwallis was appointed as governor-general and commander-in-chief of India. He remained there until 1793. Cornwallis reformed the administration in an attempt to stamp out corruption. Between 1791 and 1792 he was predominantly engaged in fighting against Tipu Sultan, ruler of Mysore. Tipu was defeated at Seringapatam in 1792 and forced to accept peace terms. In the same year, Cornwallis was created a Marquess.
Cornwallis returned to Britain in 1793. In 1795, in the face of the French Revolutionary Wars, he was appointed as master-general of the ordnance with a seat in the Cabinet. In 1797 he was once again appointed as governor-general of India, but he did not take up this position. Instead, in 1798, he was appointed Lord Lieutenant (Viceroy) and commander-in-chief in Ireland. Cornwallis worked closely with Viscount Castlereagh, the Chief Secretary to Ireland, to bring about the Act of Union between Great Britain and Ireland, which was passed in 1800. Both resigned in 1801 over the King's refusal to grant emancipation to Catholics, which they had thought would be linked to the achievement of the Union.
In 1805 Cornwallis returned to India as governor-general, but within two months he contracted a fever and died.