His first work was done as assistant to Sir A.H. Layard in his first expedition (1845-1847). He subsequently came to England, studied at Oxford (Magdalen College), and was again sent by the British Museum trustees to accompany Layard in his second expedition (1849-1851).
Layard having entered upon a political career, Rassam continued the work (1852-1854) in Assyria under the direction of the British Museum and Sir Henry Rawlinson at Nimrud and Kuyunjik. In 1866 he was sent by the British government to Abyssinia, where, however, he was imprisoned for two years until freed by the victory of Sir Robert Napier.
From 1876 to 1882 he was again in Assyria conducting important investigations, especially at Nineveh, and during the Russo-Turkish War he went on a mission of inquiry to report on the condition of the Christian communities of Asia Minor and Armenia. His archaeological work resulted in many important discoveries and the collection of valuable epigraphical evidence.