After a cadetship at the Royal Military Academy at Woolwich, near London, Chesney was gazetted to the Royal Artillery in 1805 and later rose to be a general. During a tour of military duty at Constantinople (now Istanbul) in 1829, he formulated plans for the Suez Canal that were the basis of Ferdinand de Lesseps (Lesseps, Ferdinand, vicomte de)' undertaking completed in 1868.

Chesney undertook a survey of the Euphrates River. In the late 1820s the East India Company was actively looking for a faster route to India. Company officials were considering either a route through Egypt or a more direct route through what is now Syria, Iraq, and the Persian Gulf. After a daring journey from ʿĀnah on the Euphrates River to the Persian Gulf, Chesney in 1831 suggested the construction of a railway that would link the Persian Gulf to the navigable portion of the Euphrates, thereby opening the fast, economical, and direct route to India. With the support of the India board, the body that oversaw the affairs of British India, he pressed the proposal on the British government. In 1835 he was sent in command of a small expedition to test the navigability of the Euphrates. In spite of much opposition from the Egyptian pasha, he transported two steamers in sections overland from the Mediterranean at Antioch to the middle Euphrates. The Tigris went down in a storm, but Chesney and the Euphrates reached the Persian Gulf in the summer of 1836. Though the voyage was deemed a success, the British government took no steps to implement his plan. His report of the expedition was published in The Expedition for the Survey of the Rivers Euphrates and Tigris, 2 vol. (1850), and Narrative of the Euphrates Expedition (1868).

Chesney was sent to Hong Kong (1843–47) to command the British artillery after the first Opium War with China. He retired from the army in 1847, and, though he went to the Middle East again in 1856 and 1862, he made his home in Ireland until his death.