Background: COVID-19 is an emergent infectious disease that has spread geographically to become a global pandemic. While much research focuses on the epidemiological and virological aspects of the COVID-19 transmission, there remains a gap in knowledge regarding the drivers of geographical diffusion between places. Here, we use quantile regression to model the roles of globalisation, human settlement and population characteristics as socio-spatial determinants of COVID-19 diffusion over a six-week period in March and April 2020. Results: The quantile regression model suggest that globalisation and settlement population characteristics related to high human mobility predict disease diffusion. Human development level (HDI) and total population predict COVID-19 diffusion in countries with a high number of total confirmed cases per million whereas larger household size, older populations, and globalisation tied to human interaction predict COVID-19 diffusion in countries with a low number of total confirmed cases per million. Conclusions: The analysis confirms that globalisation, settlement and population characteristics lead to greater disease diffusion, and primarily variables tied to high human mobility. These outcomes serve to inform policies around ‘flattening the curve’, particularly as they related to anticipated relocation diffusion from more- to less-developed countries and regions, and hierarchical diffusion from countries with higher population and density. Epidemiological strategies must be tailored to suit the range of human mobility patterns, as well as the variety of settlement and population characteristics.