Melbourne Zoo was the first zoo established in Australia and one of the world's oldest. Its genesis dates back to a meeting assembled by F. M. Selwyn on 6 October 1857 in St. Patrick's Hall, Melbourne, for the purpose of forming an Ornithological Society. During the meeting, Dr. Thomas Black suggested that they should extend their plans and form a general Zoological Society. Subsequently the Zoological Society of Victoria was formed with the Governor of Victoria, Sir Henry Barkly, as its first patron. One of the Society's aims was to import and care for animals "of this and other countries, more particularly rare and uncommon species." The development of the Zoo was not unique and tended to parallel the establishment of a wide range of cultural institutions in the same era, notably the Public Library, the National Museum, the National Gallery and the University of Melbourne.

In 1858 a meeting was convened in the office of the Director of the Botanic Gardens and government botanist, Dr. (later Baron) Ferdinand von Meuller to discuss the creation of a zoological garden by the Society. It was conceived "for the purposes of science and for that of affording the public the advantages of studying the habits of the animal creation in properly arranged zoological gardens."

At the same time a separate Acclimatization Society had been formed by Edward Wilson, the retired editor of the Argus. Its aim included "the introduction, acclimatisation and domestication of all innoxious animals, birds, fish, insects and vegetables." As its title suggested, the Society promoted acclimatization of domestic and wild fauna rather than the display of exotic animals. The idea of adapting and introducing foxes, sparrows, blackbirds, skylarks and thrushes to alleviate the "savage silence" of the Australian bush and as a poignant reminder of England is now regarded with derision. Nevertheless the association between acclimatization and zoos became a common trend throughout Australia and would shape the Zoos that evolved in Sydney, Adelaide and Perth.

The Zoological Society and the Acclimatisation Society were amalgamated in 1861 with Wilson as the elected President and von Mueller as Vice-President. The background of the founders of the zoo, most significantly von Mueller, Wilson and Albert La Souëf, followed a trend. They were all ambitious, educated men who did not have any formal knowledge of zoology but were inspired by philanthropy and an innate appreciation for accessible, cultural institutions. In the same year as the amalgamation, the Society was given a land grant of 33 acres from the Government, commonly known as the Richmond Paddock and located opposite the Botanic Gardens. Until it was ready to receive animals, the Zoo's first collection was housed within the Botanic Gardens under the dedicated care of von Mueller. The small collection grew to consist of fauna, including monkeys, and native birds and mammals. Rumours about neglect began to circulate and it became apparent that the original site was too damp and swampy to accommodate the animals and flora. Von Mueller reluctantly requested that the Government move the Zoo and in 1862 they granted 5,5000 pounds and a 55 acre site in Royal Park.

Amid the internal bickering, Edward Wilson usurped the Zoological Society and changed its name to the Acclimatization Society of Victoria. For the remainder of the 1860s the Melbourne Zoo struggled; the logistics of transporting animals from around the world, limited resources, staffing shortages and declining public interest almost forced its closure. Considered little more than a glorified farm, the Zoo consisted of a group of deer, sheep and goats. It was in 1870 with the appointment of Albert Le Souëf as honorary secretary to the Acclimatization Society and Director of the Zoo, that its direction and potential were realized. With the purchase of a pair of lions, one leopard, some monkeys and cages for 125 pounds a solid foundation was established. The emphasis on acclimatizing animals began to wane as the need for a zoological collection to interest and educate the community dictated a new direction. Reflecting this priority, the Society changed its name in 1871 to Zoological and Acclimatization Society of Victoria, to which the prefix "Royal" was added after the grant of a Royal Charter in 1910.

In 1902 Albert Le Souëf retired, and his eldest son William Henry Dudley, followed him as Director of the Melbourne Zoo after an apprenticeship as Assistant Director. Two other sons studied veterinary medicine and worked at the Melbourne Zoo. Albert Sherbourne went on to supervise the creation of Taronga Zoo in Sydney and Ernest Albert was the foundation Director of Perth Zoo.

After the retirement of Dudley Le Souëf in 1923, the Melbourne Zoo began to experience enormous difficulties. Devoid of a guiding philosophy to aid development and the acute funding shortages (despite the imposition of a weekday entrance fee of sixpence) the Zoo's demise seemed imminent. Amid a public outcry about the atrocious conditions, facilities and rat infested cages, the Victorian Government in 1937 assumed responsibility and established the Zoological Board of Victoria as a statutory body. Despite these changes, the succeeding management continued to lack the vision and resources needed to respond to the impact of the depression and Second World War.

It was only in the 1960s with Alfred Dunbavin Butcher at the helm, that the beleaguered Zoo enjoyed a resurgence. His appointment as Chairman of the Zoological Board of Victoria was an inspired and auspicious choice. Butcher is regarded as the significant figure in developing government policy in the areas of wildlife management and environment assessment in Victoria. Perceptive and influential, Butcher instigated instrumental and profound changes notably the modernization of the animal enclosures and facilities and the introduction of an unorthodox and most active zoo education service that incorporated strong conservation and research programs. The transformation has indeed been significant, the zoo he found in 1962 was a "miserable place" of concrete and iron bars. Melbourne Zoo is now internationally recognised as one of the world's leading zoos for the scope of its educational service, richly landscaped gardens and the outstanding butterfly house.