Unsustainable wildlife trade is a major driver of biodiversity loss and an important public health threat. Yet, effective wildlife trade regulation is currently at odds with food security and economic incentives provided by this global, multibillion‐dollar industry. Given such limitations, public health and conservation resources can be aligned to target species for which trade both increases risk of extinction and threatens public health. Here, we developed a simple conservation and health trade risk (CHT) index (range: 2–50) using a case study of traded mammals based on species' extinction and zoonotic risks, weighed by the extent of their trade. We applied this index to 1161 International Union for the Conservation of Nature‐listed terrestrial mammals involved in the wildlife trade to identify 284 high‐priority species that scored high in the CHT index (CHT ≥ 18). Species ranking high for conservation, public health, and trade risks include those belonging to the orders Primates, Cetartiodactyla (even‐toed ungulates), Rodentia (rodents), Chiroptera (bats), and Carnivora (carnivores). Of the high‐priority species, 33% (n = 95) are country‐endemics and may be good candidates for trade regulations and enforcement at national scales. Our study provides a preliminary step in prioritizing species, taxonomic groups, and countries for focused wildlife trade regulation to meet both conservation and public health goals.