Significance With changes in land use and increased urbanization, the frequency with which pathogens jump species barriers to emerge in new hosts is expected to rise. Knowing which viruses may be more likely to become transmissible among humans, as opposed to only generating dead-end spillover infections, would be of considerable benefit to pandemic planning. Using multivariate modeling and multimodel inference, we sought to both identify and quantify those biological features of viruses that best determine interhuman transmissibility. This analysis revealed that chronic, nonsegmented, non–vector-borne, nonenveloped viruses with low host mortality had the highest likelihood of being transmissible among humans whereas genomic features had little predictive power. Our analysis therefore reveals that multiple virological features determine the likelihood of successful emergence.