Firestone was born in Ottawa, Canada, and raised in an orthodox Jewish family, in Saint Louis, Missouri. She attended Yavneh of Telshe Yeshivah, near Cleveland, soon switching to Washington University and the School of the Art Institute of Chicago, where she earned a BFA in painting. During her studies at the Art Institute, she was the subject of a documentary film, which was never released. The film was rediscovered in the 1990s by experimental filmmaker, Elisabeth Subrin, who did a frame-for-frame reshoot of the original documentary, with Kim Soss playing Firestone. It was released in 1997 as Shulie, winning the 1998 Los Angeles Film Critics Association award, Experimental 1999 US Super 8, a Film & Video Fest-Screening Jury Citation 2000 New England Film & Video Festival and Best Experimental Film Biennial 2002.

While living in Chicago, Firestone joined with Jo Freeman to organize the Westside Group, a predecessor of the Chicago Women's Liberation Union. In October 1967, she moved to New York and co-founded New York Radical Women, during which time she wrote three essays: "Women and the Radical Movement", "The Jeanette Rankin Brigade: Woman Power"?, and "The Women's Rights Movement in the U.S.A.: New View"When NYRW dissolved, Firestone and Ellen Willis co-founded the radical feminist group Redstockings, named after the Blue Stockings Society, a women's literary group founded by Elizabeth Montagu in the mid 18th century. Firestone left Redstockings to co-found New York Radical Feminists... In late 1968 she edited Notes from the First Year, followed by Notes from the Second Year (1970), and Notes from the Third Year (1971). By the time The Dialectic of Sex was published in 1970, she had largely ceased to be politically active. Firestone withdrew from politics in the early seventies, moved to Saint Marks Place and worked as a painter. In the late eighties she became mentally ill. In 1998 she published a haunting account of life, in and out of psychiatric hospitals, titled Airless Spaces.

In The Dialectic of Sex, Firestone synthesized the ideas of Sigmund Freud, Wilhelm Reich, Karl Marx, Frederick Engels, and Simone de Beauvoir into a radical feminist theory of politics. Firestone also acknowledged the influence of Lincoln H. and Alice T. Day's Too Many Americans (1964) and the 1968 best-seller The Population Bomb by Paul R. Ehrlich. It became a classic text in second-wave feminism in the United States.

Firestone argued that gender inequality originated in the patriarchal societal structures imposed upon women through their biology; the physical, social and psychological disadvantages imposed by pregnancy, childbirth, and subsequent child-rearing. She advocated the use of cybernetics to carry out human reproduction in laboratories as well as the proliferation of contraception, abortion, and state support for child-rearing; enabling them to escape their biologically determined positions in society. Firestone described pregnancy as "barbaric", and writes that a friend of hers compared labor to "shitting a pumpkin". Among the reproductive technologies she predicted were sex selection and in vitro fertilization.

Firestone explored a number of possible social changes that she argued would result in a post-patriarchal society, including the abolition of the nuclear family and the promotion of living in community units within a socialist society.

So that just as to assure elimination of economic classes requires the revolt of the underclass (the proletariat) and, in a temporary dictatorship, their seizure of the means of production, so to assure the elimination of sexual classes requires the revolt of the underclass (women) and the seizure of control of reproduction: not only the full restoration to women of ownership of their own bodies, but also their (temporary) seizure of control of human fertility - the new population biology as well as all the social institutions of child-bearing and child-rearing. And just as the end goal of socialist revolution was not only the elimination of the economic class privilege but of the economic class distinction itself, so the end goal of feminist revolution must be, unlike that of the first feminist movement, not just the elimination of male privilege but of the sex distinction itself: genital differences between human beings would no longer matter culturally. (A reversion to an unobstructed pansexuality Freud's 'polymorphous perversity' - would probably supersede hetero/homo/bi-sexuality.) The reproduction of the species by one sex for the benefit of both would be replaced by (at least the option of) artificial reproduction: children would born to both sexes equally, or independently of. either, however one chooses to look at it; the dependence of the child on the mother (and vice versa) would give way to a greatly shortened dependence on a small group of others in general, and any remaining inferiority to adults in physical strength would be compensated for culturally. The division of labour would be ended by the elimination of labour altogether (through cybernetics). The tyranny of the biological family would be broken.

—Shulamith FirestoneThe Dialectic of Sex

The Dialectic of Sex continues to be an influential and widely quoted feminist work. Kathleen Hanna, among others, often cites it as a critical work. The book influenced American novelist Marge Piercy's imaginative utopia, Woman on the Edge of Time. But as Hilary Rose writes, "As a socialist feminist Piercy is sensitive to issues of class; her involvement with the US radical science movement, engaged in the struggle against scientific racism, added anti-racism to her political agenda long before white feminism began to give up its taken-for-granted Eurocentricity, and gave a sophistication to her analysis of science and technology lacking in Firestone."

While some white academics in a new generation celebrate Firestone for purportedly anticipating the work of Donna Haraway, progressives and leftists like Elizabeth V. Spelman, Linda Martin Alcoff, Angela Davis, and bell hooks object to the white supremacist assumptions in Firestone's classic work. Spelman, a practitioner of critical race feminism, argues that Firestone's claim that "racism is sexism extended" encourages "white solipsism" (a term borrowed from Adrienne Rich) and is a "dangerous mistake". Spelman also investigates the white supremacist and patriarchal character of somatophobia (fear and loathing of the body) in general, a preoccupation she identifies as the principle content of The Dialectic of Sex. Progressive and socialist feminist intellectuals and activists, from Angela Davis and Margaret A. Simons in the 1970s to bell hooks in the 1990s, have criticized Firestone's work for racist contempt, fear, loathing, and abundant stereotypes, "ethnocentrism", "historical myopia" and historical innaccuracy.

Combined with an elaborate race theory developed from a metaphor of combined Freudian and Biblical origins "stretched to the breaking point and filled with ironies and stereotypes", the eugenics proposals in The Dialectic of Sex evoke a racialized vision of impending "overpopulation" which places the book in the tradition of feminist racial hygiene associated with Margaret Sanger and Charlotte Perkins Gilman:

Do the black militants who advocate unchecked fertility for black women allow themselves to become burdened with heavy bellies and too many mouths to feed? One gathers that they find contraception of some help in maintaining their active preaching schedules.

—Shulamith FirestoneThe Dialectic of Sex p. 179

The combination of Malthusian terrors of "this dangerously prolific reproduction" of "too many mouths" and the futuristic dreams of individual liberation through technology has drawn criticism to The Dialectic of Sex from neoconservatives like Midge Decter (perceiving the proposed eugenics programs as a means to attack patriarchal traditions) as well as from across the left-of-center spectrum.