Emerging infectious diseases of wildlife have markedly increased in the last few decades. Unsustainable, continuous, and rapid alterations within and between coupled human and natural systems have significantly disrupted wildlife disease dynamics. Direct and indirect anthropogenic effects, such as climate change, pollution, encroachment, urbanization, travel, and trade, can promote outbreaks of infectious diseases in wildlife. We constructed a coupled human and natural systems framework identifying three main wildlife disease risk factors behind these anthropogenic effects: (i) immune suppression, (ii) viral spillover, and (iii) disease propagation. Through complex and convoluted dynamics, each of the anthropogenic effect listed in our framework can lead, to some extent, to one or more of the identified risk factors accelerating disease outbreaks in wildlife. In this review, we present a novel framework to study anthropogenic impacts within coupled human and natural systems that facilitate emergence of infectious disease involving wildlife. We demonstrate the utility of the framework by applying it to Fibropapillomatosis disease of marine turtles. We aim to articulate the intricate and complex nature of anthropogenically-exacerbated wildlife infectious diseases as multifactorial. This paper supports the adoption of a One Health approach and invites the collaboration of multiple disciplines for the achievement of effective and long-lasting conservation and wildlife emerging diseases mitigation outcomes.