From March 2020, Whitty played a key role in the response to the COVID-19 pandemic in the UK, alongside Government Chief Scientific Adviser Sir Patrick Vallance.

During this time, with co-authors Neil Ferguson and Jeremy Farrar, he wrote an article in Nature titled "Infectious disease: Tough choices to reduce Ebola transmission",[17] explaining the UK government's response to Ebola in support of the government of Sierra Leone, which he took a leading role in designing, including the proposal to build and support centres where people could self-isolate voluntarily if they suspected that they could have the disease.

[4] During this period Novichok, the military nerve agent, was responsible for the 2018 Salisbury poisonings, and Whitty chaired the government SAGE (Scientific Advisory Group in Emergencies) and advised COBR for the crisis.

[19][20] This included appearing – often with prime minister Boris Johnson and Chief Scientific Adviser Sir Patrick Vallance – in televised news conferences, and giving evidence to parliamentary bodies.

[5][21] From 19 March, Whitty appeared in public information adverts on national television, explaining the government's social-distancing strategy to reduce the spread of the virus during the pandemic.

[21][22] On 27 March, Whitty was reported to be self-isolating owing to symptoms consistent with COVID-19 after Boris Johnson and Health Secretary Matt Hancock had tested positive for the virus.

[24] In July, he told the Lords Science and Technology Committee that elimination of the disease in the UK would be very difficult, a view that was contested by other scientists including members of the Independent SAGE group.

[26][27] Whitty and Vallance presented updated data and forecasts at a televised briefing on 31 October, where the Prime Minister announced stricter measures for the whole of England.

[28] During the outbreak, BBC health editor Hugh Pym called him "the official who will probably have the greatest impact on our everyday lives of any individual policymaker in modern times".

[32] On 27 June, Whitty was the subject of manhandling, described by Johnson as "despicable harassment", by Lewis Hughes and Jonathan Chew in St James's Park, Westminster, who filmed the event for social media.

[36] Whitty was appointed Companion of the Order of the Bath (CB) in the 2015 New Year Honours for public and voluntary service to Tropical Medicine in the UK and Africa.