MacDonald was born in Sharon, Pennsylvania, where his father, Eugene Macdonald, worked for the Savage Arms Corporation. The family relocated to Utica, New York in 1926, his father becoming treasurer of the Utica office of Savage Arms. In 1934, MacDonald was given a choice by his father: spend another year in school as a post-graduate, or go to Europe for several weeks. He chose Europe and this began an interest in travel and photography.
After graduating from high school, he enrolled at the Wharton School of the University of Pennsylvania, but he quit during his sophomore year. MacDonald worked at menial jobs in New York City, then was admitted to Syracuse University, where he met his future wife, Dorothy Prentiss. They married secretly in Pennsylvania in 1937, and had a public ceremony in Utica later that year. He graduated from Syracuse University the next year. The couple had one son, Maynard.
In 1939, MacDonald received an MBA from Harvard University. MacDonald later used his education in business and economics in crafting his fiction. Several of his novels are either set in the business world or involve shady financial or real estate deals.
In 1940, MacDonald accepted a direct commission as a first lieutenant of the United States Army Ordnance Corps. During World War II, he served in the Office of Strategic Services in the China-Burma-India Theater of Operations; this region featured in many of his earlier short stories and novels. He was discharged in September 1945 as a lieutenant colonel. Dear Dordo: The World War II Letters of Dorothy and John D. MacDonald was published by Peppertree Press in 2022.
In 1951 he moved his family from Utica, New York to Florida, eventually settling in Sarasota.
