Pathogen spillover from wildlife to domestic animals and humans, and the reverse, has caused significant epidemics and pandemics worldwide. Although pathogen emergence has been linked to anthropogenic land conversion, a general framework to disentangle underlying processes is lacking. We develop a multi‐host model for pathogen transmission between species inhabiting intact and converted habitat. Interspecies contacts and host populations vary with the proportion of land converted; enabling us to quantify infection risk across a changing landscape. In a range of scenarios, the highest spillover risk occurs at intermediate levels of habitat loss, whereas the largest, but rarest, epidemics occur at extremes of land conversion. This framework provides insights into the mechanisms driving disease emergence and spillover during land conversion. The finding that the risk of spillover is highest at intermediate levels of habitat loss provides important guidance for conservation and public health policy.