Zinkernagel qualified as an MD at the University of Basle in 1970. He moved to the Australian National University, Canberra, where he gained his PhD in 1975. Zinkernagel returned to Switzerland in 1979 to work at the University of Zurich. In 1992 he was appointed head of the Department of Experimental Immunology.

While in Canberra, when still a graduate student, Zinkernagel worked with Peter Doherty on the role of T lymphocytes and major histocompatibility complexes in fighting infection. For their work in this field they shared the 1996 Nobel Prize for physiology or medicine.