Identifying virus characteristics associated with the largest public health impacts on human populations is critical to informing “zoonotic risk” assessments and surveillance strategies. Efforts to assess zoonotic risk often use trait-based analyses to identify which viral and reservoir host groups are most likely to source zoonoses but have not fully addressed how and why the impacts of zoonotic viruses vary in terms of disease severity (“virulence”), capacity to spread within human populations (“transmissibility”), or total human mortality (“death burden”). We analyzed trends in human case fatality rates, transmission capacities, and total death burdens across a comprehensive dataset of mammalian and avian zoonotic viruses. Bats harbor the most virulent zoonotic viruses even when compared to birds, which alongside bats have been hypothesized to be special zoonotic reservoirs due to molecular adaptations that support the physiology of flight. Reservoir host groups more closely related to humans—in particular, primates—harbor less virulent but more highly transmissible viruses. Importantly, a disproportionately high human death burden, arguably the most important metric of zoonotic risk, is not associated with any animal reservoir, including bats. Our data demonstrate that mechanisms driving death burdens are diverse and often contradict trait-based predictions. Ultimately, total human mortality is dependent on context-specific epidemiological dynamics, which are shaped by a combination of viral traits and conditions in the animal host population and across and beyond the human–animal interface. Understanding the conditions that predict high zoonotic burden in humans will require longitudinal studies of epidemiological dynamics in wildlife and human populations.