This paper attempts to identify and explain patterns in the biogeography of Australia’s indigenous terrestrial mammals at the time of European settlement (before modern extinctions), and also compares species’ pre-European and current status by region. From subfossil, historical and contemporary sources, we compiled data on the past geographic range and present status of mammals for Australia’s 85 biogeographic regions. Of the 305 indigenous species originally present, 91 have disappeared from at least half of the bioregions in which they occurred before European settlement. Thirty-nine extant species ‘persist’ in less than 25% of their original bioregions; 28 of these are marsupials and 11 are rodents. Twenty-two of the original 305 species are extinct, a further eight became restricted to continental islands, and 100 have become extinct in at least one bioregion. Over the same period, 26 species of exotic mammals established wild populations and now occupy from one to 85 bioregions. When we classified the bioregions in terms of their original species composition, the 3-group level in the dendrogram approximated the Torresian, Eyrean and Bassian subregions proposed by Spencer in 1898, while the 4-group level separated southern semiarid Eyrean bioregions, including those in south-west Australia, from the arid Eyrean bioregions. The classification dendrogram showed geographically (and statistically) discrete clustering down to the 19-group level, suggesting that all four subregions can be further divided on the basis of their mammal faunas. Variation partitioning showed 66% of the biogeographical pattern can be explained by environmental factors (related to temperature and precipitation), the spatial position of each bioregion (a third-order polynomial of latitude and longitude), the area of each bioregion, and the richness of species in each bioregion. In addition to the marked distributional changes that indigenous mammals have experienced over the last 200 years, the 49% of variation explainable by temperature and precipitation implies further shifts with global climate change.