Donna Dennis was born in 1942 in her maternal grandparents' house in Springfield, Ohio, the eldest of four girls. She attended public schools there and in Washington, D.C. until her family, including her grandparents, moved to Rye, New York in 1949. There she attended Milton School and later, Rye High School, graduating in 1960.

She cannot remember a time when she did not want to be an artist. As a child she drew and painted all the time, and was encouraged by her teachers and her parents, especially, her mother. Her favorite game as a child was a universal one - making a "house" out of almost anything – boxes, blankets, branches – and crawling inside. Especially inspiring was a snapshot of her mother as a child standing at the door of an igloo made by her uncle after an Ohio snowstorm. Her mother had wanderlust and the family took month-long, vaguely planned car trips every summer. These were better than Christmas. Frequently, the family spent the night in slightly run-down tourist cabins – the only available accommodation after the more modern motels had lit up the "No" on the neon "Vacancy" sign out front. Donna hated the cabins, preferring the motels with their swimming pools, but they left her with vivid memories of both intimacy and alienation. One trip to Boston when she was six or seven included a visit to the Old North Church of Paul Revere fame. At the time, the church seemed run down and forgotten. She remembers being shocked and feeling the same sort of sadness for the building that she would feel for a person in a similar situation.

At Rye High School, Donna continued to receive encouragement for her art, especially from teacher Mabel D'Amico, an artist who exhibited in New York. During her high school years she created sets for several student productions and in the senior year book she was described as "our poet and artist". Donna has often turned to poetry and fiction for inspiration and keeping journals is an important part of her work process, helping her to develop the metaphorical content of her work. A critic once called her "a poet of infrastructure."

At Carleton College she majored in art, focusing on painting and took lots of literature courses. The year after graduation, she spent in Paris with Martha Diamond, a fellow art major at Carleton and explored the city and its cultural milieu with two other Carleton classmates, Peter Schjeldahl and his then wife, Linda O'Brien. In Paris, she studied painting with an American sculptor, Roger Barr, in a classroom at the top of the American Center on the Boulevard Raspail.

Returning from Paris, Donna settled in New York City, working full time by day and attending the Art Students' League at night. Peter introduced her to his circle of poet friends centered around the Poetry Project at St. Mark's Church, including Ted Berrigan, who, at the time, was also an art critic. She later came to think of Ted as her mentor.

In the late 1960's she began to move from painting toward sculpture without realizing that was where she was headed. By the early 1970's she was making painted false front "hotel" facades which she thought of as shaped canvases. Although she was drawn to some sculptors; Bontecou, Flavin, Tony Berlant, her inspiration came mostly from painters: Hopper, De Chirico, Matisse, Magritte, Burchfield, Dine, and photographers: Atget, Walker Evans, Berenice Abbott, Wright Morris. She also loved Joseph Cornell.

The women's movement gave her both a larger purpose that was liberating and the courage to draw on her own early experiences. She remembers reading Virginia Woolf's A Room of One's Own as crucial in developing the central metaphor of her work: finding women's voice and placing it in the world.

In 1973 she had her first one-woman show "Hotels" at a co-op gallery in Soho. The hotels were set up like a tropical village with bird calls and hot lights. The slightly reduced scale of the work, a scale she uses to this day, was derived from her own body: the first hotel was 68" tall and the top of the front door came to her eye level.

In 1975 the collector Holly Solomon asked Donna to join the gallery she was starting and in 1976 she had her first show there, "Subway Stations and Tourist Cabins". In the late 1970's her work began to become more widely known. She exhibited at the Walker Art Center in 1977 and in 1979 she was in both the Whitney Biennial and the Hirshhorn Museum's "Directions". In 1975 she was awarded a Creative Artists Public Service grant, the first of many grants to follow, including several NEA's and a Guggenheim.

In the 1980's her work began to be seen internationally, including at the Venice Bienale in 1982 and 1984, the Tate Gallery and Ludwig Forum fur Internationale Kunst, Aachen, Germany. Then, in the late 1980's and the 1990's, while continuing to create and exhibit large architecturally-inspired installations, she also completed a number of permanent public art commissions in New York and Boston. Over the years she has also collaborated with poets (Ted Berrigan, Anne Waldman, Kenward Elmslie) and with performers (Dan Hurlin). She is a Professor of Art at Purchase College, State University of New York.