On 17 December 1915 Mackerras enlisted in the Australian Imperial Force after advancing his age.
From January 1927 he worked at the Bureau of Microbiology of the New South Wales Department of Public Health.
Mackerras served in the Middle East and Guinea in World War II, advising on sanitation and malaria.
On 2 June 1947 Mackerras became the first Director of the newly established Queensland Institute of Medical Research (QIMR) in Brisbane.
In 1950 Mackerras was awarded the Clarke Medal by the Royal Society of New South Wales; was elected a fellow of the Australian Academy of Science at its first election in 1954, and served on its Council from 1955 to 1957; he and wife Josephine were both appointed as Research Fellows in the Division of Entomology, in the Commonwealth Scientific and Industrial Research Organisation in August 1961.