In 1986, on assignment from the CDC, Berkley served as an epidemiologist for the Massachusetts Department of Public Health, working on routine surveillance and outbreak investigations.

Berkley played a role in helping to develop Uganda's National AIDS Control programs, and served as an attending internal medicine physician at Mulago Hospital in Kampala.

Subsequently, Berkley worked for the Rockefeller Foundation, initially as program scientist and finally as associate director of the Health Sciences Division.

These meetings, culminating in a conference in Bellagio, Italy, became the impetus for the establishment of IAVI in 1996 as an international NGO tasked with aggressively pursuing previously neglected approaches to AIDS vaccine development.

[10] Gavi is a public-private partnership whose mission is to save children's lives and protect people's health by increasing access to immunisation in developing countries.

Berkley and Coalition for Epidemic Preparedness Innovations (CEPI) CEO Dr. Richard Hatchett were involved in founding COVAX, the global COVID-19 pandemic vaccine initiative, following a meeting at the World Economic Forum in Davos.

[14] Berkley has sat on a number of international steering committees and corporate and not-for-profit boards, including those of Gilead Sciences, the New York Academy of Sciences, the Acumen Fund, the Council of Foreign Relations,[15] the Scientific Advisory Panel assisting the UNAIDS High Level Commission on HIV Prevention,[6] Oxfam America, the Guttmacher Institute, VillageReach, VaxInnate, PowderJect, Napo pharmaceuticals[16] and the US National Academy of Medicine.