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Iannone was born in Boston, Massachusetts in 1933. She graduated from Boston University in 1957 with a B.A. in American Literature. She went on to study English Literature at the graduate level at Brandeis University. In 1958 she married the painter James Upham and the couple moved to New York City. In 1959, she begins to paint. From 1961 till 1967, she travels intensively in Europe and the Far East with her husband. They live and work often for several months in, among other places, southern France and Japan. From 1963 till 1967 she runs with her husband the Stryke Gallery, Tenth Street, New York. In 1961 she successfully sued the United States Government on behalf of Henry Miller's book Tropique du Cancer (roman), which until then was censored in the U.S, to allow its importation into the country. She moves to Berlin in 1976 after receiving a grant from the DAAD Berlin Artists' program. She still lives and works in Berlin, where she pursues her artistic production.
Dorothy Iannone's œuvre, which now spans more than fifty years, includes painting and visual narrative, autobiographical texts and films. Since the 1960s she has been seen as a pioneering spirit against censorship and for free love and autonomous female sexuality. She continues to go her own way without compromise, artistically and conceptually 
Dorothy Iannone’s great theme is ecstatic love. The paintings, visual narratives, texts and books by this pioneer of women’s sexual and intellectual emancipation draw uncompromisingly on her own life. Iannone’s art frequently fell foul of the censors because of allegedly pornographic content. And yet her depictions of the sexual union between man and woman have an unmistakably mystical dimension rooted in the spiritual and physical union of opposites. This anchors her visual universe within cultural history and lends a modern, personal interpretation to Eastern religions, including TibetanBuddhism, IndianTantrism and Christianecstatic traditions like those of the seventeenth-century Baroque from 17th
The explicit nature of Iannone's work frequently fell foul of censors in the 60s, 70s, and 80s. The artist said of the early censorship of her work: "When my work was not censored outright, it was either mildly ridiculed or described as folkloric, or just ignored." In 1969 the Kunsthalle Bern tried to censor Iannone's work in the group exhibition Ausstellung der Freunde by requesting that she cover up the genitals of her figures. In protest Dieter Roth dropped out of the exhibition and the curator of the Kunsthalle Bern, Harald Szeeman, resigned. Iannone recalled the experience in the Fluxus publication The Story of Bern or Showing Colors (1970).
Iannone's first solo exhibition in the US, Lioness, was held at the New Museum in 2009. Her work has been featured in numerous group and solo exhibitions across Europe throughout her life. In 2007, Air de Paris has exhibited a selection of paintings, drawings and sculptures in a show titled: "She Is A Freedom Fighter". In 2013, "Innocent And Aware": a retrospective of Dorothy Iannone's works has been organized at Camden Art Center London. In 2014, Berlinische Galerie in Berlin and "Migros Museum" in Zurich have both programmed a retrospective of her work.
On a trip to Reykjavik, Iceland in 1967, Iannone met the Swiss artist Dieter Roth. Iannone separated from her husband one week later. Iannone lived with Roth in Düsseldorf, Reykjavik, Basel and London until 1974. Roth became Iannone's muse and features in much of her artwork. His nickname for her was "lioness." She said of her work at this time: "The two of us became the stars of my work." One of her most noted works involving Roth is her book An Icelandic Saga(1978-86), which vividly illustrates the artist's first encounter with Roth and her subsequent breakup with her husband in the vein of a Norse myth. She also created paintings of her and Roth in sexual union. Titled Eros Paintings, Iannone develops her own cosmos of images that revolves around the philosophical concept of Eros. Implicit in this concept is the idea that human beings are deeply moved by a yearning for union. Desire is therefore conceived as a supremely natural force whose wellspring is love, ecstasy and the dissolution of ego – a human striving toward physical-spiritual unity. Iannone and Roth remained friends until his death in 1998.