Sustainable use of wildlife is a core aspiration of biodiversity conservation but is the subject of intense debate in the scientific literature, including the extent to which use is impacting species and whether management can mitigate any impact. Although positive and negative outcomes of sustainable use are known for specific taxa or local communities, a global and regional picture of trends in wildlife populations in use is lacking. We use a global dataset of more than 11,000 time series to derive indices of “utilized” and “not utilized” wildlife populations. Our results show that population trends globally are negative on average but that utilized populations tend to decline more rapidly, especially in Africa and the Americas. Crucially, where populations are managed, they are more likely to be increasing. This evidence can inform global biodiversity assessments and provide an operational indicator to track progress toward the Post-2020 Global Biodiversity Framework.