Ferguson has used mathematical modeling to provide data on several disease outbreaks: 2001 United Kingdom foot-and-mouth outbreak, swine flu outbreak in 2009 in the UK, the 2012 Middle East respiratory syndrome coronavirus outbreak and the ebola epidemic in Western Africa in 2016. His work has also included research on mosquito-borne diseases including zika fever, yellow fever, dengue fever and malaria.
In February 2020, during the 2019–2020 coronavirus pandemic, which began in China, Ferguson and his team used statistical models to estimate that cases of coronavirus disease 2019 (COVID-19) were significantly under-detected in China. He is part of UK's Imperial College COVID-19 Response Team. On 18 March 2020, he reported that he had developed the symptoms of COVID-19, and self-isolated.