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In February 2020, during the COVID-19 pandemic, which was first detected 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.

As of February 2020, at Imperial College, London, he was a professor of mathematical biology, director of the Abdul Latif Jameel Institute for Disease and Emergency Analytics (J-IDEA), head of the Department of Infectious Disease Epidemiology in the School of Public Health and Vice-Dean for Academic Development in the Faculty of Medicine.

As of March 2020, Ferguson was a member of the UK Department of Health advisory body called the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG), which advises the CMOUK.

One of Ferguson's models predicted that 65,000 people could die from swine flu. In the event, no more than 500 died. Health Secretary Matt Hancock was questioned about the prediction during the Today programme on 16 April 2020.

In February 2020, during the COVID-19 pandemic (ongoing as of March 2020), using statistical models that considered data on the number of deaths and recoveries inside China, travellers outside China and in those affected that had returned home, Ferguson, Azra Ghani and their team estimated that detected cases of COVID-19 had significantly underestimated the actual spread of the disease in China. That month he stated that only 10% of cases were being detected in China. At the same time, it was noted that the number of available testing kits had come into question, and Ferguson calculated that only one in three cases coming into the UK was being detected. He stated "that approximately two-thirds of cases in travellers from China have not yet been detected. It is highly likely that some of these undetected cases will have started chains of transmission within the countries they entered." He said that the new coronavirus could affect up to 60% of the UK's population, in the worst-case scenario, and "suggest(ed) that the impact of the unfolding epidemic may be comparable to the major influenza pandemics of the twentieth century." His team's publication in mid-March of the projections that the UK could face hundreds of thousands of deaths from COVID-19 without strict social distancing measures, gained widespread media attention. In late March, he calculated that with "strict social distancing, testing and isolation of infected cases", deaths in the UK could fall to less than 20,000.

On 5 May 2020, it emerged that Ferguson had resigned from his position as a government advisor on the Scientific Advisory Group for Emergencies (SAGE) committee after admitting to "undermining" the government's messages on social distancing by meeting up with a married woman. The Telegraph reported that the woman had visited his home at least two times. After resigning, Ferguson said "I acted in the belief that I was immune, having tested positive for coronavirus and completely isolated myself for almost two weeks after developing symptoms", adding that he regretted undermining "clear messages" about the need for social distancing. The Secretary of State for Health and Social Care, Matt Hancock, said that he was right to resign from his advisory position. Ferguson did not receive a fine or prosecution for his actions.

Ferguson reported on 18 March 2020 that he had developed the symptoms of COVID-19, and self-isolated. He recovered after a mild illness. Ferguson is married and has one son.

Together with a number of other persons, in 2016 he proposed a World Serum Bank as a means of helping combat epidemics.

In 2016, he co-authored a paper titled "Countering the Zika epidemic in Latin America", published in Science. Although disputed by at least one other biostatistician, Ferguson and his team concluded that the age distribution of future outbreaks of zika will likely differ and that a new large epidemic would be delayed for “at least a decade”. Cases of zika dropped after 2016. That year, he predicted that the zika outbreak in the Americas would be over within three years, and clarified that "viruses tend to return when there are enough susceptible people, such as children, to sustain a new outbreak".

Wolbachia is a bacterium frequently found in insects but not in the Aedes aegypti mosquito, which carries the dengue virus. In 2015, Ferguson published a paper titled "Modeling the impact on virus transmission of Wolbachia-mediated blocking of dengue virus infection of Aedes aegypti", in which he and his team presented their experiments and used a mathematical model to show that one strain of Wolbachia, could reduce the ability of the Aedes aegypti mosquito to transmit dengue, with a 66-75% reduction in the basic reproduction number.

In 2014, as the director of the UK Medical Research Council's centre for outbreak analysis and modelling at Imperial, Ferguson provided data analysis for the WHO, on Ebola during the ebola epidemic in Western Africa. In the same year, he co-wrote a paper with Christopher J. M. Whitty published in Nature and titled "Infectious disease: Tough choices to reduce Ebola transmission", explaining the UK government's response to ebola in Sierra Leone, including the proposal to build and support centres where people could self-isolate voluntarily if they suspected they had the disease.

In 2013, he contributed to research on MERS-CoV during the first MERS outbreak in the Middle East, and its link with dromedary camels.

Ferguson's research has raised questions by virologist Hendrik Streeck. Ferguson is the corresponding author for a paper titled "Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand", which describes itself as having "informed policymaking in the UK and other countries in recent weeks". Streeck stated in reference to the paper "In the – really good – model studies by the Imperial College about the progress of the epidemic, the authors assume, for example, that 50 percent of households in which there is a case do not comply with the voluntary quarantine. Where does such an assumption come from? I think we should establish more facts." The computer models on which Ferguson relied were criticized as "unreliable."

During the swine flu outbreak in 2009 in the UK, in an article titled "Closure of schools during an influenza pandemic" published in the Lancet Infectious Diseases, Ferguson and colleagues endorsed the closure of schools in order to interrupt the course of the infection, slow further spread and buy time to research and produce a vaccine. Ferguson's team reported on the economic and workforce effect school closure would have, particularly with a large percentage of doctors and nurses being women, of whom half had children under the age of 16.

In the House of Lords Science and Technology Committee's "follow-up" to the swine flu epidemic in 2009, Ferguson recommended that to halt transmission of swine flu, actions would need to include "treating isolated cases with antivirals, public health measures such as school closures, travel restrictions around the region, mass use of antiviral prophylaxis in the population and possible use of vaccines". He was also asked why there was not a policy for vaccinating frontline healthcare workers at that time.

Ferguson and colleagues founded the Medical Research Council (MRC) Centre for Global Infectious Disease Analysis in 2008. He advises the World Health Organization (WHO), the European Union, and the governments of the UK and United States, on the dynamics of infectious disease. He is an international member of the National Academy of Medicine, a fellow of the Royal Statistical Society, and is on the editorial boards of PLOS Computational Biology and Journal of the Royal Society Interface. He is a founding editor of the journal Epidemics.

Ferguson was appointed an Officer of the British Empire (OBE) in the 2002 New Year Honours for his work modelling the 2001 United Kingdom foot-and-mouth outbreak. He was elected a Fellow of the Academy of Medical Sciences (FMedSci) in 2005. He is also an International Member of the US National Academy of Medicine.

Ferguson has used mathematical modelling to provide data on several disease outbreaks including the 2001 United Kingdom foot-and-mouth outbreak, the 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.

During the 2001 United Kingdom foot-and-mouth outbreak Ferguson worked on the team, led by Roy M. Anderson of Imperial College, creating mathematical models used to inform the UK Government of the most effective methods of preventing the spread of foot-and-mouth-disease. Ferguson published a journal article in Science magazine in April 2001 describing the mathematical models that were relied upon by the UK government to recommend the mass slaughter of millions of cows, sheep and pigs in the UK in order to stop the spread of the disease; over a decade later, the BBC would remind its readers Ferguson "was among those advising government on how to control the epidemic a decade ago."

Ferguson was part of Roy Anderson's group of infectious disease scientists who moved from the University of Oxford to Imperial College in November 2000, and started working on modelling the 2001 United Kingdom foot-and-mouth outbreak a few months later.

He received his Master of Arts degree in Physics in 1990 at Lady Margaret Hall, Oxford and his Doctor of Philosophy degree in theoretical physics in 1994 at Linacre College, Oxford. His doctoral research investigated interpolations from crystalline to dynamically triangulated random surfaces and was supervised by John Wheater.

Neil Morris Ferguson OBE FMedSci (born 1968) is a British epidemiologist and professor of mathematical biology, who specialises in the patterns of spread of infectious disease in humans and animals. He is the director of the Abdul Latif Jameel Institute for Disease and Emergency Analytics (J-IDEA), head of the Department of Infectious Disease Epidemiology in the School of Public Health and Vice-Dean for Academic Development in the Faculty of Medicine, all at Imperial College, London.

They studied previous influenza pandemics including the 1918 flu pandemic, the influenza pandemic of 1957 and the 1968 flu pandemic. They also looked at the dynamics of the spread of influenza in France during French school holidays and noted that cases of flu dropped when schools closed and re-emerged when they reopened. They noted that when teachers in Israel went on strike during the flu season of 1999–2000, visits to doctors and the number of respiratory infections, fell by more than a fifth and more than two-fifths respectively.