Grumbach was born in New York City to Leonard William and Helen (Oppenheimer) Isaac. She grew up in Manhattan and attended elementary school there as a very bright student who skipped many grades and entered high school at age eleven. She was not prepared socially for this early advancement and did poorly, developing a stammer and losing her self-confidence. She was encouraged by her teachers to take a year off from high school, and when she returned a year later, she was an indifferent student in the classroom but showed talent in theater and in creative writing. In her senior year, she won a citywide short story contest, which helped secure her admission to Washington Square College of New York University. She majored in philosophy and graduated Phi Beta Kappa, receiving her B.A. degree in 1939. She earned her M.A. degree in medieval literature in 1940 from Cornell University.
At Cornell, she met her future husband, Leonard Grumbach, who was a doctoral student in neurophysiology. They were married on October 5, 1941, and during 1940-41, Grumbach worked for Loew's, Inc./MGM writing subtitles for films distributed abroad. During 1941-42, she was employed as a proofreader for Mademoiselle magazine and then for the journal Architectural Forum in 1942-43, eventually rising to the position of associate editor. When her husband was drafted during World War II, Grumbach joined the Navy in 1943 as an officer in the WAVES (Women Accepted for Volunteer Emergency Service). She served in the Navy from 1943-45.
After the war, Grumbach followed her husband around the country as he pursued a career in physiology. During this period, the Grumbachs had four daughters: Barbara, Jane, Elizabeth, and Kathryn. Before the birth of their fourth daughter, the Grumbachs settled in Albany, New York, where Leonard Grumbach taught at Albany Medical College and Doris Grumbach began a career in teaching. From 1957-60, she taught junior and senior English at the Albany Academy for Girls. In 1960, she became a professor of English at the College of Saint Rose and taught there until 1971. During her time at the College of Saint Rose, Grumbach also began to focus on her writing career and published her first two novels, The Spoil of the Flowers (1962), and The Short Throat, The Tender Mouth (1964).
In 1971, after raising her children, Grumbach left her husband and spent a year in Saratoga Springs, New York helping to set up the external degree program at Empire State College. In 1972, she divorced her husband and began a relationship with Sybil Pike, who became and remains her life partner. Also in 1972, Grumbach accepted a position at The New Republic magazine as literary editor. Later she moved to Washington, D.C., and worked for a magazine for two years until the magazine was sold and she lost her job. She remained in Washington and in 1975 accepted a position as professor of American literature at American University. During this time, she also wrote a nonfiction column for The New York Times Book Review. Her writing career continued, and in 1976 she published a literary biography of novelist Mary McCarthy titled The Company She Kept. The biography was noteworthy and controversial for its use of correspondence and other documents that McCarthy had shared with Grumbach, McCarthy’s her long-time friend, but had never intended to be made public, let alone published.
In 1979, Grumbach published the novel, Chamber Music, which was critically well received and helped establish her reputation as a novelist. In six years, three more books followed: The Missing Person (1981), The Ladies (1984), and The Magician's Girl (1987). During this period Grumbach also taught creative writing at the Writers Workshop at the University of Iowa and at Johns Hopkins University, where she worked with such writers of note as John Irwin, John Barth, Edward Albee, and Jennifer Finney Boylan. Grumbach also was a book reviewer and commentator for the “Morning Edition” of National Public Radio and the televised McNeil-Lehrer Newshour.
In 1985, Grumbach resigned her professorship at American University but remained in Washington, D.C. for five more years. She and her life partner, Sybil Pike, opened a bookstore for rare and used books named Wayward Books. In 1990 Grumbach and Pike moved their bookstore and themselves to Sargentville, Maine where Grumbach continues to live and write.
Several facets of Grumbach’s work have won her both praise and criticism. Grumbach is often lauded as a feminist writer championing the cause of women in her fiction and revealing the economic, social, and psychological difficulties women face. Other critics, though, find her work not feminist enough and regard her portrayals of women characters as stilted. In a similar vein, Grumbach is highly regarded and often criticized for her focus on gay and lesbian characters. A number of her works, like The Spoil of the Flowers, Chamber Music, and The Ladies, focus on gay and lesbian themes and characters. Noteworthy, too, especially for the era in which Grumbach began writing, is that she presents lesbian and gay characters in a positive light...a fact that often mobilizes social critics against her for what they perceive to be an unconventional, if not immoral, stance.
Another aspect of Grumbach's work to draw both praise and criticism is that Grumbach writes in such a wide range of genres...a feature that may raise questions along the lines of "jack of all trades, but master of none." However, a counter argument may be that Grumbach shows interesting talents and a myriad of literary skills to be able to write as a novelist, literary critic, essayist, biographer, memoirist, and cultural critic.
As a writer who explored gay and lesbian themes in the 1950s and 1960s, Grumbach tends to be grouped with other groundbreaking authors who explored these themes and issues at a time in which the popular sentiment was to regard homosexuality as deviant behavior. Such writers as Ann Bannon, Marijane Meaker, Sylvia Townsend Warner, and Patricia Highsmith explored gay and lesbian themes in positive ways similar to Grumbach. As Ann Cothran, a literary critic of writers on lesbian themes and author of a study on Simone de Beauvoir states, perhaps Grumbach’s “most important contribution to gay and lesbian literature is the manner in which she consistently represents homosexual relationships matter of factly, as an integral part of the human landscape. Grumbach depicts lesbianism as a positive, life-giving force in women's lives.” 
Grumbach’s novels also tend to be literary and literate in tone in that she often draws upon well-known writers or writings for her titles and for references within her works. For example, she drew her title for The Spoil of the Flowers from a poetic fragment by Euripides, the title for The Short Throat, The Tender Mouth from "The Pardoner’s Tale" in The Canterbury Tales by Geoffrey Chaucer, and The Magician’s Girl from a poem by Sylvia Plath. In addition, Grumbach’s writings often reference well known or arcane writings and also in the dialogue or in an internal monologue phrases from Latin, French, and other languages.
One aspect of Grumbach’s novels that drew positive critical attention was her use of actual persons and events as the basis for her fictionalized presentations. In Chamber Music, for example, she bases the characters and the plot on the American composer Edward MacDowell and his wife, Marian; upon Marilyn Monroe in The Missing Person; upon Eleanor Butler and Sarah Ponsonby in The Ladies; and Sylvia Plath and Diane Arbus in The Magician’s Girl.
Interestingly, given Grumbach’s achievements as a novelist, a significant part of her reputation and her current audience is based upon her two memoirs that focus upon aging: Coming into the End Zone and Extra Innings. She has also received praise for her spiritual reflections about her life in The Presence of Absence: On Prayers and an Epiphany. Grumbach also remained an important literary critic by writing introductions and critical assessments to the works of such writers as Willa Cather, Edith Wharton, and Zora Neale Hurston. Grumbach also wrote an influential review of the novel Wise Blood by Flannery O’Connor and an article on an aborted plan to write a biography of Willa Cather, which was published in the American Scholar journal of the Phi Beta Kappa society in January 2001.
Overall, while Grumbach never attained the stature of other writers in the last half of the twentieth century, she remains an important author for the focus she brought to women’s lives and women’s struggles in the redefinition of women’s roles from the 1950s onward. This dimension is especially true with regard to her positive presentations of lesbians and lesbian lifestyles. Grumbach is also admired for her writing style and characterization, which often presents overtones of Henry James and of Gustave Flaubert and Jane Austen in Grumbach’s focus upon social conventions and their influence upon the development of individual lives and psyches. Grumbach is one of several twentieth-century women writers, such as Sylvia Townsend Warner, Valentine Ackland, and Katherine Mansfield who represent a transition from Victorian styles and emphases combined with the social and psychological concerns of modernism. Grumbach’s papers (from 1938 to 2002) are archived in the New York Public Library (Humanities and Social Sciences Library, Manuscripts and Archives Division).