In a career that spanned more than four decades, Howe's best-known works include Museum, The Art of Dining, Painting Churches, Coastal Disturbances, and Pride's Crossing.

Her grandfather, Mark Antony De Wolfe Howe, published over 50 books and won the Pulitzer Prize for Biography in 1925.

'"[10] When Howe was ill with hepatitis, her father visited her every day in the hospital, reading James Joyce's Ulysses to her during his lunch break.

In his book Contemporary American Playwrights, Bigsby wrote that she had a "commitment to experimentation" and quotes Howe as saying said that she is "firmly entrenched in the Absurdist tradition.

"[17] Frank Rich, in his New York Times review of Painting Churches commented that the play "is in the dreamiest impressionistic spirit.

In this case joie de vie, despair, love, lust, anger and fear come and go like the waves hitting the shore in foamy bursts or gentle ripples.

"[24] Howe's first full-length play to receive a professional production was The Nest, which premiered in summer 1969 at the Act IV Theater in Provincetown, Massachusetts.

The Nest, Clive Barnes of The New York Times wrote in his review, "must be on any reasonable short list of the worst plays I have ever seen.

"[27] Her play Museum, with a cast of 55 characters, premiered at the Los Angeles Actors' Theatre on April 29, 1976,[28] and was then presented Off-Broadway by Joseph Papp at the Public Theater, opening in February 1978, in a production directed by Max Stafford-Clark.

"[31] In her note in the script (published by Samuel French), Howe wrote: "It is my hope that any group wanting to present Museum use the large cast size as a challenge and not as a restriction.

[33] Howe herself won an Obie Award in 1983 for distinguished playwriting for her plays The Art of Dining, Museum and Painting Churches.

[40] It was revived off-Broadway by the Keen Company in March 2012, directed by Carl Forsman, starring Kathleen Chalfant, John Cunningham, and Kate Turnbull.

[46] This was followed by Approaching Zanzibar, which shows the Blossom family traveling across the United States to visit Olivia, a sick relative.

The play premiered at the Second Stage Theatre on April 8, 1989, directed by Carole Rothman, and starred Jane Alexander as Charlotte Blossom, Harris Yulin as her husband, Angela Goethals as her daughter and Bethel Leslie as her dying aunt.

The reviewer for The Independent wrote: "... a zany, expertly mimed sequence throws the tensions of cooped-up family car travel into rollicking relief when, in fantasy, the parents and children swap roles.

[15][54] Howe wrote English translations of Eugène Ionesco's The Bald Soprano and The Lesson, which were produced at the Atlantic Theater Company in September 2004.

[55] The plays were directed by Carl Forsman and featured Jan Maxwell, John Ellison Conlee, Michael Countryman and Robert Stanton.

[57] The play was first presented at the Wilma Theatre (Philadelphia, Pennsylvania) in September 1995, after being rewritten and having readings, and a workshop at the California State University Summer Arts Festival.

Howe's brilliant mind is teeming with enough ideas to fill several plays, and her themes and style at times suggest an early fascination with older playwrights such as Ionesco and Albee.

The play takes place in a nursing home, with the "rebellious painter" and a Jewish woman becoming friends and planning on escaping to go to Paris aboard the QE2.

[61] Her full-length play Singing Beach premiered Off-Broadway at HERE Arts Center on July 22, 2017, in previews in a limited engagement, produced by Theatre 167.

Directed by Ari Laura Kreith, the cast featured Erin Beirnard, Devin Haqq, Jackson Demott Hill, John P. Keller, Tuck Milligan, Elodie Morss, and Naren Weiss.

[62] Howe's plays have been produced in regional theatres in the United States, such as Louisville,[52] Los Angeles,[29] Stockbridge, Massachusetts,[20] Annapolis, Maryland [63] and San Diego,[51] as well as in London.

At the ceremony in November 2017 at the Gershwin Theatre, she was introduced by her long-time friend Jane Alexander, who said "She has passion, wit and absurdity.... [her plays are an] operatic dive into the depths.... She writes as no one else does about women..."[88]