[1] In the 1960s, she was an active participant in New York City's downtown art scene, collaborating with influential artists such as John Cage and Marcel Duchamp.

Knowles's inclusion of visual, aural, and tactile elements sets her art apart from the work of other Fluxus artists.

Many of the Fluxus leaders, such as Dick Higgins, George Brecht, Al Hansen and Allan Kaprow, took the historic class.

[5] Knowles's focus in painting diminished after her show at the Nonegon Gallery in New York, in which she destroyed all of her works in a bonfire behind her brother's house.

Unlike a traditional bound volume, the pages of this work are tiny paper scrolls, which the reader may select and view in any order.

On each scroll, Knowles printed found texts collected from songs, recipes, stories, science, cartoons, and advertisements.

In 1967, Knowles created The House of Dust, perhaps the most widely known example of computer-generated digital poetry, in collaboration with composer James Tenney.

Selecting a phrase from each list would describe a house made of a certain material, in a particular location, illuminated by a light source, and sheltering various inhabitants.

[8][9] She gave the lists to Tenney, who generated the printed poetry using the FORTRAN programming language on an early IBM computer.

From roughly 10,000 possible stanzas, Knowles selected one quatrain—“a house of dust / on open ground / lit by natural light / inhabited by friends and enemies”—as the basis for an interactive sculpture on the California Institute of the Arts campus in the early 1970s.

The book traveled to cities in Canada, Europe, and the United States, gradually disintegrating into its individual components by the time it reached its final destination in San Diego, California.

[14] “It was about having an excuse to get to talk to people, to notice everything that happened, to pay attention,” said Knowles during her recent rendition of the event score at the Museum of Modern Art.

[20] Knowles's interest in the sounds produced by beans was explored in a series of four radio programs hosted by the German station Westdeutscher Rundfunk, whose director was a friend and supporter of John Cage.

Although she changed direction as her interest in performance developed, Knowles began producing silkscreen paintings shown at the Judson Gallery in the early 1960s.

In 1963, she collaborated with Cage students Robert Watts and George Brecht in the Scissors Brothers Warehouse show, commonly referred to as BLINK for the bold word that appears in the center.

Initially, Knowles wanted the rights to reproduce the image for the cover of a Something Else Press publication (featuring Emmett Williams's concrete poem Sweethearts).

In 2015 Knowles was selected by the art historian Claire Bishop to receive a Francis J. Greenburger Award, which go to under-recognized artists every two years.

Knowles often does performance pieces with members of her family, including Loose Pages, Shoes Of Your Choice, and Beans All Day.