The 2017 IUCN Red List of Threatened Species includes ca. 6000 species of mammals, approximately 500 species more than in the last complete mammal assessment published in 2008. This dataset provided the basis for the calculation of the Red List Index (RLI), which is an indicator of the aggregated risk of extinction of a group of species. The 2017 RLI was compared to the RLI in 1996 and 2008, the two years for which complete mammal assessments are available, providing a 21-year trend in extinction risk for the world’s mammals. For large mammals (carnivores and ungulates), the RLI backcasted to 1975 allowed the extension of the comparison across a 42-year period. The RLI of all mammals, as well as that of large mammals, showed a steady decrease over time, with far more species moving towards extinction than species averting extinctions at any time-step considered. Several iconic species and subspecies, including the eastern gorilla, Bornean orangutan, plains zebra, and lowlands tree kangaroo are now at higher risk of extinction that nine years ago. Despite conservation efforts and some conservation success, increasing pressures on biodiversity continue to drive the decline of mammals globally.