Within her time in the free thought movement in the early 1880s, de Cleyre was influenced by Thomas Paine and Mary Wollstonecraft especially, and also Henry David Thoreau, Big Bill Haywood, Clarence Darrow, and later Eugene Debs. After the hanging of the Haymarket martyrs in 1887, however, she became an anarchist. "Till then I believed in the essential justice of the American law of trial by jury," she wrote in a 1914 autobiographical essay, "After that I never could."

De Cleyre was known as an excellent speaker and writer — in the opinion of Paul Avrich, her biographer, she was "a greater literary talent than any other American anarchist" — and as a tireless advocate for the anarchist cause, whose "religious zeal," according to Goldman, "stamped everything she did.... Her whole nature was that of an ascetic."

Voltairine de Cleyre was esteemed by Emma Goldman and wrote an essay in her defense. However, the two women disagreed on some essential points: "Miss Goldman is a communist; I am an individualist. She wishes to destroy the right of property, I wish to assert it. I make my war upon privilege and authority, whereby the right of property, the true right in that which is proper to the individual, is annihilated. She believes that co-operation would entirely supplant competition; I hold that competition in one form or another will always exist, and that it is highly desirable it should."

For several years De Cleyre associated herself with the American individualist anarchists and adopted the philosophy. In her 1894 essay In Defense of Emma Goldman and the Right of Expropriation, de Cleyre wrote in support of the right of expropriation while remaining neutral on its advocacy: "I do not think one little bit of sensitive human flesh is worth all the property rights in N. Y. city... I say it is your business to decide whether you will starve and freeze in sight of food and clothing, outside of jail, or commit some overt act against the institution of property and take your place beside TIMMERMANN and GOLDMANN."

Eventually, however, de Cleyre was moved to reject individualism as well: "Socialism and Communism both demand a degree of joint effort and administration which would beget more regulation than is wholly consistent with ideal Anarchism; Individualism and Mutualism, resting upon property, involve a development of the private policeman not at all compatible with my notion of freedom."

Instead she became one of the most prominent advocates of "anarchism without adjectives," a movement in anarchism which focused on harmony between the various factions and did not advocate anything beyond the basic conception of anarchism as anti-state and anti-capitalist. In The Making of an Anarchist, she wrote, "I no longer label myself otherwise than as 'Anarchist' simply."

She ended by embracing anarchist communism, arguing in "Why I am an Anarchist" that "the best thing ordinary workingmen or women could do was to organise their industry to get rid of money altogether . . . Let them produce together, co-operatively rather than as employer and employed; let them fraternise group by group, let each use what he needs of his own product, and deposit the rest in the storage-houses, and let those others who need goods have them as occasion arises." In 1912 she argued that the Paris Commune, while "making war upon the State, she had not made war upon which creates the State . . . the Commune respected property . . . [and] had left common resources in private hands . . In short, though there were other reasons why the Commune fell, the chief one was that . . . the Communards were not Communists. They attempted to break political chains without breaking economic ones." ("The Commune Is Risen")

This, however, in no way contradicted her support for anarchism without adjectives as communist-anarchists, including Peter Kropotkin and Errico Malatesta, always stressed that in an anarchist society people who did not want to live as communists would be free to work their own land or tools.

Voltairine de Cleyre's 1912 essay in defense of direct action is widely cited today. In this essay, de Cleyre points to examples such as the Boston Tea Party, noting that "direct action has always been used, and has the historical sanction of the very people now reprobating it."

In her 1914 essay entitled Sex Slavery, Voltairine de Cleyre condemns ideals of beauty that encourage women to distort their bodies and child socialization practices that create unnatural gender roles. The title of the essay refers not to traffic in women for purposes of prostitution, although that is also mentioned, but rather to marriage laws that allow men to rape their wives without consequences. Such laws make "every married woman what she is, a bonded slave, who takes her master's name, her master's bread, her master's commands, and serves her master's passions."

Voltairine de Cleyre also adamantly opposed the standing army, arguing that its existence made wars more likely. In her 1909 essay, Anarchism and American Traditions, she argued that in order to achieve peace, "all peaceful persons should withdraw their support from the army, and require that all who wish to make war do so at their own cost and risk; that neither pay nor pensions are to be provided for those who choose to make man-killing a trade."

Voltairine de Cleyre was close to and inspired by Dyer D. Lum, "her teacher, her confidant, her comrade". On June 12, 1890 she gave birth to a son, Harry, fathered by freethinker James B. Elliot. Throughout her life she was plagued by illness and depression, attempting suicide on at least two occasions and surviving an assassination attempt on December 9, 1902. Her assailant, Herman Helcher, was a former pupil whom she later forgave, writing "It would be an outrage against civilisation if he were sent to jail for an act which was the product of a diseased brain." The attack left her with chronic ear pain and a throat infection that often adversely affected her ability to speak or concentrate.

Voltairine de Cleyre died on June 6, 1912, in Chicago, Illinois. A collection of her speeches, The First Mayday: The Haymarket Speeches, 1895-1910, was published by the Libertarian Book Club in 1980 and in 2004, AK Press released The Voltairine de Cleyre Reader, edited by AJ Brigati.