Miller was born Alma Routsong on November 26, 1924, in Traverse City, Michigan. She began college in 1942 and received an honors B.A. in art from Michigan State University in 1949. In the interim, she served two years in the U.S. Navy and married Bruce Brodie, with whom she remained fifteen years. She came out under the pen name Isabel Miller, a combination of an anagram for "lesbia" and her mother's birth name.

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Although Routsong published two novels under her own name (A Gradual Joy and Round Shape) in the 1950s, her best known work is A Place for Us, with which she introduced herself as a lesbian writer using the pseudonym Isabel Miller. Completed in 1967 and printed two years later in a 1,000-copy Bleeker Street edition that Miller financed herself, the novel was first sold on Village street corners and at meetings of the New York chapter of the Daughters of Bilitis.

In 1971, it received the American Library Association's first annual Gay Book Award. McGraw-Hill's release of the novel as Patience and Sarah one year later brought it to mainstream bookstores across the country.

Inspired by the companionship of Mary Ann Wilson and Miss Brundidge, who lived in Greene County, New York, in the 1820s, Patience and Sarah is a historical romance that typically celebrates the present by projecting its prohibitions and desires onto an idealized past.

A literary touchstone for the activism of the late 1960s and early 1970s, Patience and Sarah recounts the joyous trials of saucy, educated painter Patience White and cross-dressing farmer Sarah Dowling, who leave their native Connecticut in order to set up house together in upstate New York. There they tackle the conflict between conventional gender and sex prescriptions and unconventional behavior: Greene County becomes their green world.

Miller subsequently complicates this vision in Patience and Sarah's never completed sequel; "A Dooryard Full of Flowers," published in a 1993 collection of stories of the same name, frames the lovers' utopia not as an actual landscape but as an imaginative exercise.

Miller's writings celebrate the lesbian experiences they help define. More particularly, the lesbian representation in Patience and Sarah provides a way of reading lesbian culture. So where Miller's first novel fictionalizes history, her third historicizes that fiction.

In Side by Side (1990) artist Patricia and herbalist Sharon resemble in both name and occupation Miller's nineteenth-century heroines. Patricia attends Brundidge-Willson College. The two women belong to a lesbian group called "A Place for Us." For Miller, fiction and lesbianism are "side by side" experiences.

One of Miller's contributions to lesbian literature is her readiness to envision lesbian characters able to lead fulfilling lives. These characters may not encompass the diversity of the lesbian community. Their concerns and experiences may tend only to address white middle-class expectations. Still, to paraphrase the title of Miller's 1986 novel, for the love of good women her works are worth reading.

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It is impossible to understand twentieth-century lesbian literature without recognizing the significance of butch-femme relationships.

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From the great modernist writers of the 1920s and 1930s to the pulp writers of the 1950s to the lesbian writers of today, lesbian novelists have had a powerful impact on the lesbian community.

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The first national lesbian political and social organization in the United States, the Daughters of Bilitis was a significant part of the pre-Stonewall lesbian and gay rights movement.