On September 3, 1899, F. Macfarlane Burnet was born in the country town of Traralgon. His father, Frank Burnet, a Scottish emigrant to Australia, was the manager of the Traralgon branch of the Colonial Bank. His mother Hadassah Burnet (née Mackay) was the daughter of a middle-class Scottish immigrant, and met his father when Frank was working in the town of Koroit. Frank was 36, and 14 years older than Hadassah when they married in 1893. The family was socially conservative Anglo-Saxon Protestant. Frank Macfarlane Burnet was the second of seven children and from childhood was known as "Mac". He had an older sister, two younger sisters and three younger brothers. The eldest daughter Doris had a mental disability that consumed most of Hadassah's time and the family saw Doris's condition as an unspoken stigma, discouraging the other children from inviting friends home, lest they come across the eldest daughter.
Mac was distant from his father—who liked to spend his free time fishing and playing golf—from a young age. He preferred bookish pursuits from a young age and was not enamoured of sport, and by the age of eight was old enough to analyse his father's character; Mac disapproved of Frank and saw him as a hypocrite who espoused moral principles and put on a facade of uprightedness, while associating with businessmen of dubious ethics. Hadassah was preoccupied with Doris, so Mac developed a rather solitary personality.