Wildlife trade generates billions of dollars annually and is vital for the livelihoods of millions of people. However, it also drives species towards extinction, facilitates biological invasions, and contributes to zoonotic disease outbreaks. To ensure that wildlife trade benefits human societies without harming nature or global health, accurate evaluation of these threats and their dynamics over time is of utmost importance. Unfortunately, quantitative assessments are lacking. In this study, we analyse 180,000 records of commercial trade in wild mammals (both alive and as products) between 1980 and 2019. Controlling for phylogeny, biogeography, and research effort, we show that trade over-represents invasive and zoonotic species, while endangered species are under-represented, probably due to their protection under CITES agreements. These patterns have remained relatively stable over four decades in the product market. However, in the live animal market, while the relative intensity of trade in endangered and zoonotic species has shown a promising decline in recent decades, the over-representation of invasive species has doubled since the mid-1980s. These findings raise concerns about the effectiveness of current wildlife trade regulation systems in safeguarding both nature and people. They highlight the need for a proactive, holistic, evidence-based, and internationally coordinated regulatory strategy for the global wildlife trade.