Greenfield was born in Parmele, North Carolina and grew up in Washington, D.C. during the Great Depression in a housing project called Langston Terrace, named after John Mercer Langston, that provided a warm childhood experience for her. She was the second oldest of five children of Weston W. Little and his wife Lessie (née Jones). A shy and studious child, she loved music and took piano lessons. She graduated from Cardozo Senior High School in 1946 and attended Miner Teachers College until 1949. In her third year, however, she found that she was too shy to be a teacher and dropped out.

Greenfield began work in the civil service at the U.S. Patent Office. In 1950, she married World War II veteran Robert J. Greenfield, a long-time friend. She began writing poetry and songs in the 1950s while working at the Patent Office, finally succeeding in getting her work published after many years of writing and submitting poetry and stories. After joining the District of Columbia Black Writers Workshop in 1971, she began to write books for children. She has published more than 40 children's books, including picture books, novels, poetry and biographies. She says that she seeks to "choose and order words that children will celebrate".

Dismayed by the depiction of blacks and black communities in popular media, Greenfield has focused her work on realistic but positive portrayals of African-American communities, families and friendships. These relationships are emphasized in Sister (1974) a young girl copes with the death of a parent with the help of other family members, Me and Nessie (1975) about best friends, My Daddy and I (1991) and Big Friend, Little Friend (1991) about mentoring. Her first book, Bubbles (1972), "sets the tone for much of Greenfield's later work: Realistic portrayals of loving African American parents working hard to provide for their families, and the children who face life's challenges with a positive outlook." In She Come Bringing Me that Little Baby Girl (1974), a boy deals with feelings of envy and learns to share his parents’ love when his baby sister arrives. The poignant Alesia (1981) concerns the bravery of a girl handicapped by a childhood accident. Night on Neighborhood Street (1991) is a collection of poems depicting everyday life in an urban community. One of her best-known books, Honey I Love, first published in 1978, is a collection of poems for people of all ages concerning the daily lives and loving relationships of children and families. Her semi-autobiographical book Childtimes: A Three-Generation Memoir (1979) describes her happy childhood in a neighborhood with strong positive relationships. In the introduction to that book, she explains her interest in biography:

People are a part of their time. They are affected, during the time that they live by the things that happen in their world. Big things and small things. A war, an invention such as radio or television, a birthday party, a kiss. All of these help to shape the present and the future. If we could know more about our ancestors, about the experiences they had when they were children, and after they had grown up, too, we would know much more about what has shaped us and our world.

In 1971, Greenfield began work for the District of Columbia Black Writers' Workshop, as co-director of adult fiction and then, in 1973, as director of children's literature. That group's goal was to encourage the writing and publishing of Africa-American literature. She was writer-in-residence at the District of Columbia Commission on the Arts and Humanities in 1985-86 and taught creative writing in schools under grants from the Commission. She has also lectured and given free workshops on writing of African-American children's literature. She is a member of the National Literary Hall of Fame for Writers of African Descent and a member of the African-American Writers Guild. Since 1991, most of Greenfield's books have been illustrated by Jan Spivey Gilchrist.

In 1983, Greenfield won the Washington, DC Mayor's Art Award in Literature. In 1990 she received a Recognition of Merit Award from the George G. Stone Center for Children's Books in Claremont, California. She won the Award for Excellence in Poetry for Children, given by the National Council of Teachers of English. She also received a lifetime achievement citation from the Ninth Annual Celebration of Black Writing, Philadelphia, PA, 1993; the Virginia Hamilton Literary Award; the Milner Award; the Hope S. Dean Award from the Foundation for Children's Literature; the American Library Association notable book citation; and the National Black Child Development Institute Award, among others.

Greenfield lives in Washington, D.C. She and her husband have a son, Steve, a daughter, Monica, and four grandchildren.

• Bubbles (1972, illustrated by Eric Marlow, later reprinted as Good News)
• She Come Bringing Me that Little Baby Girl (1974, illustrated by John Steptoe; winner of the Irma Simonton Black Award, Bank Street College of Education)
• Sister (1974, illustrated by Moneta Barnett; winner of The New York Times Outstanding Book of the Year citation)
• Me and Neesie (1975, illustrated by Moneta Barnett)
• First Pink Light (1976, illustrated by Barnett)
• Africa Dream (1976, illustrated by Carole Byard; winner of the Coretta Scott King Award)
• I Can Do It by Myself (1978, with her mother, Lessie Jones Little, illustrated by Byard)
• Talk About a Family (1978, illustrated by James Calvin)
• Darlene (1980, illustrated by George Ford)
• Grandmama's Joy (1980, illustrated by Byard)
• Grandpa's Face (1988, illustrated by Floyd Cooper)
• Big Friend, Little Friend (1991, illustrated by Jan Spivey Gilchrist)
• I Make Music (1991, illustrated by Gilchrist)
• Lisa's Daddy and Daughter Day (1991, illustrated by Gilchrist)
• My Doll, Keshia (1991, illustrated by Gilchrist)
• My Daddy and I (1991, illustrated by Gilchrist)
• Koya DeLaney and the Good Girl Blues (1992)
• Aaron and Gayla's Alphabet Book (1993, illustrated by Gilchrist)
• William and the Good Old Days (1993, illustrated by Gilchrist)
• Sweet Baby Coming (1994, illustrated by Gilchrist)
• Honey, I Love (1995 picture book, illustrated by Gilchrist)
• On My Horse (1995, illustrated by Gilchrist)
• Easter Parade (1998, illustrated by Gilchrist)
• The Friendly Four (2006, illustrated by Gilchrist)
• Brothers & Sisters (2008, illustrated by Gilchrist)

Biographies and non-fiction

• Rosa Parks (1973, illustrated by Eric Marlow; winner of the 1974 Carter G. Woodson Book Award from the National Council for the Social Studies)
• Paul Robeson (1975, illustrated by Ford; winner of the 1976 Jane Addams Children's Book Award)
• Mary McLeod Bethune (1977, illustrated by Pinkney)
• Childtimes: A Three Generation Memoir (1979, with L. J. Little, illustrated by Jerry Pinkney))
• Alesia (1981, with Alesia Revis, illustrated by Ford, with photographs by Sandra Turner Bond)
• For the Love of the Game: Michael Jordan and Me (1997, illustrated by Gilchrist)
• How They Got Over: African Americans and the Call of the Sea (2003, illustrated by Gilchrist)

Poetry

• Honey, I Love and Other Poems (1978, illustrated by Leo and Diane Dillon; winner of the Recognition of Merit Award)
• Daydreamers (1981, illustrated by Tom Feeling)
• Nathaniel Talking (1988, illustrated by Gilchrist)
• Under the Sunday Tree (1988, illustrated by Amos Ferguson)
• Night on Neighborhood Street (1991, illustrated by Gilchrist)
• Angels (1998, illustrated by Gilchrist)
• I Can Draw a Weeposaur and Other Dinosaurs (2001, illustrated by Gilchrist)
• In the Land of Words (2004, illustrated by Gilchrist)