Born in Germany, the couple actually met in Brazil, where Hans was a salesman and Margret had gone to escape the rise of Nazism. They married in 1935 and moved to Paris that same year.

While in Paris, Hans's animal drawings came to the attention of French publisher, who commissioned him to write a children's book. The result, i, is little remembered today, but one of its characters, an adorably impish monkey named Curious George, was such a success that the couple considered writing a book just about him. Their work was interrupted with the outbreak of World War II. As Jews, the Reys decided to flee Paris before the Nazis seized the city. Hans built two bicycles, and they fled Paris just a few hours before it fell. Among the meager possessions they brought with them was the illustrated manu.

The Rey's odyssey brought them to the Spanish border, where they bought train tickets to Lisbon. From there they returned to Brazil, where they had met five years earlier, but this time they continued to New York. The books were published by Houghton Mifflin in 1941, though certain changes had to be introduced because of the technology of the time. Hans and Margret originally planned to use watercolors to illustrate the books, but since they were responsible for the color separation, he changed these to the cartoon-like images that continue to feature in each of the books. (A collector's edition with the original watercolors was recently released.)

i was an instant success, and the Reys were commissioned to write more adventures of the mischievous monkey and his friend, the Man in the Yellow Hat. They wrote seven stories in all, with Hans mainly doing the illustrations and Margret working mostly on the stories, though they both admitted to sharing the work and cooperating fully in every stage of development. At first, however, Margret's name was left off the cover, ostensibly because there was a glut of women already writing children's fiction. In later editions, this was corrected, and Margret now receives full credit for her role in developing the stories.

The Reys moved to Cambridge, Massachusetts in 1963, in a house close to Harvard Square, where they lived until their deaths. After her husband's death in 1977, Margret continued writing, and in 1979, became a Professor of Creative Writing at Brandeis University in Waltham, Massachusetts.

Whether they are aware of it or not, millions of amateur astronomers see the constellations through Rey's eyes. Before the 1952 publication of Rey's i (ISBN 0395248302) star charts used a conventional set of diagrams that seemed arbitrary, were hard to remember, and relied on dim stars that, regrettably, are hard to see today in populated areas. Rey invented a new set of constellation diagrams that corresponded to what could be seen from a suburban backyard on an ordinary night. He was successful in finding shapes that could really be seen as cartoonish depictions of the creature or character the constellations was supposed to represent—or, at least, were memorable. His constellation diagrams were widely adopted and now appear in many astronomy guides, such as Menzel's i are still in print.

In 1989 Margret Rey established the Curious George Foundation to help creative children and prevent cruelty to animals. In 1996, she made major to the Boston Public Library and Beth Israel Deaconess Medical Center. She was also a long-time supporter of the Longy School of Music.