McCullough studied at Sydney University to be a doctor but soon found she had an allergic skin reaction to the antiseptic soap used by surgeons. Changing careers to neurophysiology, McCullough eventually found work in the esteemed Great Ormond Street Hospital in London, England. She was eventually recruited as a researcher at the Yale Medical School, residing in America from 1967 to 1976. In later years McCullough would return to Sydney to help establish the neurophysiology department at the city's Royal North Shore Hospital.
Attracted to storytelling since the age of five, Colleen McCullough gave it up temporarily when her beloved brother Carl died at age twenty-five while saving two drowning women off the coast of Crete (Carl was said to have been the inspiration for the character Dane in "The Thorn Birds"). Yet when her Yale colleague Erich Segal gathered enormous publicity for his novel "Love Story," the thirtysomething McCullough decided to try writing again. Her second published novel was "The Thorn Birds."
McCullough's later work included the "Masters of Rome" series, nine novels that so thoroughly depicted the ancient city that MacQuarie University in Sydney bestowed on her a Doctor of Letters degree in 1993. Colleen McCullough apparently never forgot her time in the United States in that her output included a series of mystery novels featuring Carmine Delmonico, a detective in 1960s Connecticut.

McCullough's last novel, "Bittersweet," describing the lives and loves of four sisters in Depression-era Australia, was published in 2013. In addition to "Bittersweet" and other books cited in this article, Merrick Library also stocks the following works of Colleen McCullough:
Antony and Cleopatra
Caesar: Let the Dice Fly
Caesar's Women
A Creed for the Third Millenium
The First Man in Rome
The Grass Crown
An Indecent Obsession
Morgan's Run
Naked Cruelty
The October Horse
On, Off
The Prodigal Son
Sins of the Flesh
The Song of Troy
Too Many Murders
The Touch
