Hume was born on his father's property at Seven Hills near Parramatta, a settlement close to (and now a suburb of) Sydney. His father was Andrew Hamilton Hume, who came to Australia in 1790 as a superintendent of convicts and soon afterwards became a free settler. There were few opportunities for education in Australia during the first ten years of the nineteenth century, and Hamilton Hume received most of his education from his mother.
When only 17 years of age, he began exploring the country beyond Sydney as far to the south-west as Berrima, and soon developed into a good bushman. In March 1817 he went on a journey with James Meehan, the deputy surveyor-general, during which Lake Bathurst and the Goulburn Plains were discovered. Subsequently he went with John Oxley and Meehan to Jervis Bay, and in 1822 was with the party which sailed down the east coast in search of rivers.
In 1824 Hume was seen by Governor Brisbane with reference to an expedition to Spencer Gulf. Brisbane was also in touch about this time with William Hovell on the same subject, but it is not quite clear who was the first approached. Difficulties arose about the financing of the journey and eventually the two men decided to make the journey at their own expense, except for some packsaddles, arms, clothes and blankets, which were provided from government stores. Hume, in a letter dated 24 January 1825, (immediately after the return of the explorers), practically claimed to have been the leader of the party. He refers to "the expedition your Excellency was pleased to entrust to my care". But Brisbane did not accept this view of it, as in a letter to the secretary, Wilmot Horton, dated 24 March 1825 he mentions the "discovery of new and valuable country . . . by two young men Messrs Hovell and Hume . . . they were directed by me to try and reach Spencer's Gulf". It may also be pointed out that in the letter to Brisbane of 28 July 1824, Hovell signed first. These facts are of interest in view of the controversy which broke out many years later. Each of the explorers brought three assigned servants with him and between them they had five bullocks, three horses and two carts. Nearly the whole of the journey was through heavy mountain country, and there were several rivers to be forded. The courage, resource and bushmanship of Hume were important factors in surmounting their many difficulties, and after a journey of 11 weeks they came to Corio Bay near the present site of Geelong. Here, possibly through faulty instruments, Hovell made a mistake of one degree in his observation, and they believed that they were on the shore of Western Port. The return journey for some time was made on a course more to the west, the country was more level, and they were back at their starting point less than five weeks later. Their provisions were finished just before the end of the journey, and the whole party was very near exhaustion. Hume and Hovell each received grants of of land, an inadequate reward for discoveries of great importance made by an expedition which, practically speaking, paid its own expenses. This expedition discovered the overland route between Sydney and Port Phillip Bay, on whose shores Melbourne now stands.
In November 1828, Hume journeyed with Charles Sturt into western New South Wales, where they discovered the Darling River, the Murray River's longest tributary. Hume was able to communicate with some aborigines they met early in their journey who consented to act as guides, and later, when the aborigines left them, Sturt speaks with appreciation of Hume's ability in tracking their animals which had strayed. Being a drought year, it was a constant struggle to find water, and only good bushmanship saved the party. Sturt would have liked Hume to go with him on his second expedition, which started at the end of 1829, but he had a harvest to get in and was unable to make arrangements. He had finished his work as an explorer, and spent his remaining days as a successful pastoralist.
In December 1853 an imperfect report of a speech Hovell had made at Geelong was the cause of much feeling between the two men. Hume had always regarded himself as the real leader of their joint expedition, and his indignation lost all bounds at the thought of Hovell minimizing his share in the work. Fuller reports of the speech show that this was not the case, but the vehemency of Hume and his friends at the time led to the work of Hovell being underrated for a long period. Hume published in 1855 A Brief Statement of Facts in Connection with an Overland Expedition from Lake George to Port Phillip in 1824, which went into three editions. Hovell published two pamphlets Reply to "A Brief Statement of Facts in Connection with an Overland Expedition from Lake George to Port Phillip in 1824", and an Answer to the Preface to the Second Edition of Mr Hamilton Hume's "A Brief Statement of Facts", (for a balanced discussion of the merits of the case see paper by professor Sir Ernest Scott in Journal and Proceedings of the Royal Australian Historical Society, vol. VII).
Hume was an excellent explorer, a first-rate bushman never lacking in courage and resource, whose work was not adequately appreciated or rewarded by the government of the time. He had a good knowledge of some of the local aboriginal people, was always able to avoid conflicts with them, and appears to have learnt something of their speech. He has an established and well-deserved reputation as a great Australian explorer.
Hume later served as a magistrate in Yass until his death at Yass on 19 April 1873. He married a Miss Dight who survived him without children. He is sometimes stated to have been the author of The Life of Edward John Eyre, but the Hamilton Hume who wrote this book lived in London.
The Hume and Hovell expedition is commemorated by the Hume Highway, the principal road between Sydney and Melbourne. Hume and Hovell were also commemorated by having their portraits printed on the Australian one-pound banknote between 1953 and 1966.