The museum began with the natural history collection of Edward Smith-Stanley, the 13th Earl of Derby - a man who kept the largest private menagerie in Britain at his Knowsley estate east of Liverpool. When Stanley died in 1851 he left the collection to the town: 20,000 birds, mammals, and reptiles, including many specimens collected for him by Edward Lear, the nonsense poet who paid the rent by drawing exotic parrots for the Earl. The collection went into a new building on Duke Street and was called the Derby Museum. It outgrew that home almost immediately. A competition for a combined museum and college of technology was won by Edward William Mountford in the late 1890s, and the College of Technology and Museum Extension opened in 1901, expanding the museum into the William Brown Street ensemble of civic buildings - alongside the Walker Art Gallery, the William Brown Library, St George's Hall, and Wellington's Column - that remains one of the densest concentrations of Victorian municipal architecture in Britain.

In 1867 a Liverpool goldsmith and antiquarian named Joseph Mayer donated over 5,000 Egyptian antiquities to the museum. Mayer had bought up pieces from the great early-nineteenth-century Egypt collectors - Henry Salt, Joseph Sams, Lord Valentia, Bram Hertz - and displayed them in his own private Egyptian Museum on Colquitt Street so that Liverpudlians could see what the British Museum held in London. His donation made Liverpool, in the words of Egyptologist Amelia Edwards, "the most important collection of Egyptian antiquities in England next to the contents of the British Museum." The collection was then enlarged through subscription to twenty-five excavations in Egypt and Sudan between 1884 and 1914, and through the work of Liverpool University's Professor John Garstang, who dug at Meroe and Abydos and brought finds home. The collection now spans the prehistoric to the Islamic period and includes major holdings from Abydos, Amarna, Beni Hasan, Esna, and Meroe. The mummy room is one of the most popular galleries.

In May 1941, at the height of the Liverpool Blitz, an incendiary bomb fell on the museum. The building burned to a shell. The Egyptian galleries, the physical sciences gallery, the gallery of economic botany, almost all of it - gone. Not everything was lost. Large parts of the collection had been crated and moved out at the start of the war. Some of the Earl of Derby's original mammals survived. Most of the cabinet bird skins survived. But it would not be until 1976 that the Egyptian gallery was permanently reinstated in the rebuilt museum, and the physical sciences collection had to be assembled essentially from scratch. The post-war rebuilding allowed the museum to take in important university and regional collections - Liverpool University placed substantial Egyptian material here in 1955, and in 1956 Liverpool acquired almost the entire non-British collection of the Norwich Castle Museum. A 35-million-pound refurbishment in 2005 doubled the display space, added the six-storey atrium, and brought the museum back to civic centrality.

The current World Museum is designed to be navigated by children. The Bug House - opened during the 2005 refurbishment - displays living colonies of leaf-cutter ants, scorpions, and tarantulas under glass. The Weston Discovery Centre lets visitors handle natural-history specimens. The Clore Natural History Centre has interactive drawers and microscopes. The planetarium - one of the only public planetariums in northwest England - draws around 90,000 people a year. The aquarium on a lower floor displays Mediterranean and tropical fish. And in a quiet corner of the reserve collection, behind glass, sits the only specimen of the Spotted Green Pigeon in existence. Known locally as the Liverpool pigeon, it is presumed extinct - probably an inhabitant of Tahiti or one of the nearby Pacific islands - and this skin, brought to Liverpool perhaps in the late eighteenth century, is the entire physical evidence of the species. The museum also holds a great auk egg, a thylacine skin, a Falkland Islands wolf, and a dodo - a small private catalogue of what humans have already lost.