Benary-Isbert was born in Saarbrücken, Germany. She attended the College St. Carolus and the University of Frankfurt. She worked as a secretary at the Museum of Ethnology and Anthropology in Frankfurt, Germany from 1910—1917. She married Wilhelm Benary in 1917. They settled in Erfurt, living in an old family farm house in the country. While her husband attended to the family business, she raised Great Danes. USM de Grummond Collection — MARGOT BENARY-ISBERT PAPERS

When the Russians took over Germany, she fled to the apartment of a friend in West Germany. In 1948 she wrote Die Arche Noah (The Ark). Post-war Germany became a common theme in most of her works.

In 1952 she moved to the United States, where she worked as a writer until her death in 1979. She received American citizenship in 1957.

Most of Benary-Isbert's books were written and published originally in German; some were later translated into English and published again.

Benary-Isbert is known for her "depictions of humane, realistic characters". A reviewer for the Times Literary Supplement wrote that, "Benary's people are people; they are solid, real characters and their lives and their hopes and their sorrows matter to the reader." Her narratives are admired for being richly detailed and of a consistently high quality, perhaps higher than many other books in the same genre of the time.

Margot Benary-Isbert died on May 27, 1979, in Santa Barbara, California.