Human activities are driving climate, land cover, and population change (global change), and shifting the baseline geographical distribution of snakebite. The interacting effects of global change on snakes and communities at risk of snakebite are poorly understood, limiting capacity to anticipate and manage future changes in snakebite risk. In this modelling study, we projected how global change will affect snakebite envenoming incidence in Sri Lanka, as a model system that has a high incidence of snakebite. We used the shared socioeconomic pathway (SSP) scenario analysis framework to integrate forecasts across the domains of: climate change (historical trend from WorldClim plus three underlying regional circulation models [RCMs] in the Coordinated Regional Downscaling Experiment-South Asia repository, with two emissions pathways [representative concentration pathways RCP4.5 and RCP8.5]); land cover change (Dyna-CLUE model); and human population density change (based on Gridded Population of the World data) from Jan 1, 2010 to Dec 31, 2050. Forecasts were integrated under three different development scenarios: a sustainability pathway (SSP1 and no further emissions), a middle-of-the-road pathway (SSP2 and RCP4.5), and a fossil-fuelled pathway (SSP5 and RCP8.5). For SSP2 and SSP5, we nested three different RCMs (CNRM-CM5, GFDL-CCM3, and MPI-ESM-LR; mean averaged to represent consensus) to account for variability in climate predictions. Data were used as inputs to a mechanistic model that predicted snakebite envenoming incidence based on human-snake contact patterns. From 2010 to 2050, at the national level, envenoming incidence in Sri Lanka was projected to decrease by 12·0-23·0%, depending on the scenario. The rate of decrease in envenoming incidence was higher in SSP5-RCP8.5 than in SSP1 and SSP2-RCP4.5. Change in envenoming incidence was heterogenous across the country. In SSP1, incidence decreased in urban areas expected to have population growth, and with land cover changes towards anthropised classes. In SSP2-RCP4.5 and SSP5-RCP8.5, most areas were projected to have decreases in incidence (SSP5-RCP8.5 showing the largest area with incidence reductions), while areas such as the central highlands and the north of the country showed localised increases. In the model, decreases occurred with human population growth, land use change towards anthropised classes (potentially shifting occupational risk factors), and decreasing abundance of some snake species, potentially due to global warming and reduced climatic and habitat suitability, with displacement of some snake species. Snakebite envenoming incidence was projected to decrease overall in the coming decades in Sri Lanka, but with an apparent emerging conflict with sustainability objectives. Therefore, efforts to mitigate snakebite envenoming incidence will need to consider the potential impacts of sustainability interventions, particularly related to climate and land use change and in areas where increases in incidence are projected. In view of global change, neglected tropical diseases and public health issues related to biodiversity, such as snakebite, should be managed collaboratively by both environment and health stakeholders. UK Medical Research Council.