Jean Merrill was born on January 27, 1923, in Rochester, New York. She is the daughter of Earl and Elsie Almetta Merrill. Merrill grew up in Webster, New York, along the shores of Lake Ontario where the out-of-doors played a great role in her maturation. She would tell Contemporary Authors Online that her "interest in writing children's books may have derived from the great impact certain books had on [her] as a child, and perhaps a wish to recreate the quality of that experience." Following graduation from high school, Merrill matriculated at Allegheny College in Meadville. She earned her BAin English and Theatre in 1944, graduating Phi Beta Kappa. She then earned a master's degree from Wellesley College in 1945.

Though she would gain fame as a children's writer, Jean Merrill began her career after Wellesley as an editor for Scholastic Magazines, from 1945 to 1949. She then moved to editorial positions at Literary Cavalcade in 1950. During her first stay at Literary Cavalcade, she began to publish children's works, including Henry, The Hand-Painted Mouse in 1951 and The Woover in 1952. Merrill left the magazine for several years, beginning in 1952 when she held a Fulbright Fellowship at the University of Madras in India, studying folklore. She would eventually write several books with Asian folklore at their heart: Shan's Lucky Knife (Burmese, 1960), The Superlative Horse (Chinese, 1961); and The Girl Who Loved Caterpillars (Japanese, 1992). Following her return from India, she again worked for Literary Cavalcade and then for the Publications Division of the Bank Street College of Education until devoting herself entirely to writing for children.

Though she wrote a number of books throughout the 1950s and early 1960s, including the Lewis Carroll Shelf Award-winning book The Superlative Horse, Merrill's great success came with 1964's The Pushcart War. The story is written in the guide of a formal history that looks back to the events of the Pushcart War, a war set ten years after the publication date. Set in New York, it putatively addresses the issue of traffic congestion in the great metropolis caused by ever-increasingly large trucks that demand (and feel entitled to) mastery of the roads. The first to feel the wrath of the trucking companies are the iconic pushcart vendors of New York. Instead of fleeing, however, the pushcart proprietors fight back, using pea shooters to puncture the tires of the Mighty Mammoths, the Ten-Ton Tigers, and the Leaping Lemas (the largest of the trucks). After a series of conflicts with such colorful names as "The Daffodil Massacre," "The Secret Campaign," and "The Pea Shooter Campaign" led by Morris the Florist, Frank the Flower, Harry the Hot Dog and General Anna, the pushcart operators defeat the trucking interests and reduced the number and size of trucks in the City. Ruth Hill Viguers wrote in the Horn Book's original review of The Pushcart War that she felt it was "both humorous and downright funny" the end result of which would be "once a boy or girl discovers it, the new will spread." Alberta Eiseman of the New York Times praised the book, saying "it's rare indeed to find a book for young people with both a point of view and a sense of the ridiculous." The book was awarded the Lewis Carroll Shelf Award for 1965. The Times Literary Supplement (London) would praise the book's continued relevance in 1973 upon its first British publication.

In 1969, Merrill published The Black Sheep. It tells the story of Basalt, a black sheep with a taste for gardening who is born amongst a society of white sheep who shear themselves and knit sweaters from the wool to keep warm. Eventually Basalt's non-conformity drives the white sheep to banish him from their society. The rigid conformity of the society, however, becomes increasingly unwieldy and drives them to accept both Basalt and freedom of thought. Natalie Babbitt wrote in the New York Times Book Review that "Jean Merrill brings off a difficult thing...her fable is a satisfying sandwich in which the peanut butter, sticky and nourishing, slides down with ease due to judicious use of jelly."

Merrill published The Toothpaste Millionaire in 1972. It tells the tale of two sixth graders, Rufus Mayflower and Kate Mackinstrey, in East Cleveland. Rufus, the title character, is a self-reliant and inventive young African American who "doesn't seem to mind that [Kate is] black and he's black. He doesn't even mind that [she's] a girl." Together, they build an incredibly successful toothpaste company that threatens the major corporations with their low prices and honesty. In addition to the themes related to race, gender, and business, Merrill subtly weaves a number of math word problems into the plot of the story. Betty Boegehold wrote in the St. James Guide to Children's Writers that The Toothpaste Millionaire, like The Pushcart War, showed the "favorite theme of Merrill—the struggle of the small and weak against the strong and mighty." Virginia Haviland wrote in the Horn Book that "It requires exceptional talent to make engrossing a story with so plain a purpose" and Booklist particularly praised the depiction of Rufus. The Toothpaste Millionaire became an ABC Afternoon Special in 1974.

Merrill's last work was a retelling of a 12th century Japanese tale: The Girl Who Loved Caterpillars. It is the story of Izumi, the daughter of an official in the court of the Emperor. Unlike a "proper" girl of the period who should be enamored of butterflies, Izumi spends her time with caterpillars. For a time she attracts the interest of a young nobleman; he eventually finds he cannot make a relationship with such an unusual girl. The story breaks off suddenly, following the original medieval manuscript whose second chapter has been lost. Most reviewers, Kate McClelland in the School Library Journal, Betsy Hearne in the Bulletin of the Center for Children's Books, and the reviewer for Kirkus Reviews, all praised Merrill's style, though Publisher's Weekly found the abrupt ending disconcerting.

Merrill's best-known work, The Pushcart War, has been updated over the years to maintain the feel of the tale being a history. When issued in 1964, the "history" was set in 1976; when re-issued in 1974, it was set in 1986. The 1985 edition was set in 1996. In 1990, Dartmouth literature professor Noel Perrin began his column "Rediscoveries for Children" in the Washington Post with The Pushcart War, writing that "this semi-recognized classic is one of the funniest and most satisfying triumphs of small-and-clever I know. It can be read in four different ways, and they are all funny." In the summer of 2006, Edric Haleen premiered a musical adaptation of the novel in Holt, Michigan, a version Merrill reportedly praised for its faithfulness to the original book.

Jean Merrill died in 2012.