She was born to a middle class Jewish family in the Five Towns area of Long Island. Her father was a largely unsuccessful businessman and organized crime associate. She later claimed that the social milieu shown in the movie Goodfellas (some of which was set in the Five Towns area) bore some resemblance to her own childhood. As a teenager, she turned towards drugs and the counterculture, and was a hanger-on to New York countercultural musicians such as The Fugs. Relocating to East Village during her college years, she began studying art at The Cooper Union.
In 1968, she married her first husband, Carl Kominsky, with whom she relocated to Tucson, Arizona. Their marriage did not last long. However, she retained the surname Kominsky after their split. During this time, she attended University of Arizona, graduating with a BFA in 1971. She was also introduced to Spain Rodriguez and Kim Deitch by former Fugs drummer Ken Weaver, who was living in Tucson at the time. Spain and Deitch introduced her to underground comics, inspiring her to begin writing underground comics herself and to relocate to San Francisco.
Soon after arriving in San Francisco, she was introduced to Robert Crumb by mutual friends, who noted an uncanny resemblance between her and the coincidentally-named Crumb character Honeybunch Kaminski. Their relationship soon became serious and they began living together not long after. She also fell in with the Wimmen's Comix collective, and contributed to the first issue of that series. After she and Diane Noomin had a falling out with Trina Robbins and other members of the collective, they started their own title, Twisted Sisters. Kominsky-Crumb has later claimed that a large part of her break with the Wimmen's Comix group was over feminist issues and particularly over her relationship with Robert Crumb, whom Robbins particularly disliked.
Aline married Robert Crumb in 1978. Their daughter Sophie Crumb was born in 1981. Since the late 1970s, she and Robert have produced a series of collaborative comics called Dirty Laundry (also known as Aline & Bob's Dirty Laundry), a comic about the Crumb family life. Each of them drew his or her own characters for the comic. Later installments of Dirty Laundry feature contributions by Sophie, who also began producing comics in her teens.
For several years during the 1980s, she was editor of Weirdo, a leading alternative comics anthology of the time, taking over editorship from Peter Bagge, who had taken over from original editor Robert Crumb.
She was featured in a number of scenes in Crumb, the 1994 documentary about the Crumb family. Since the early 1990s, she and Robert have lived as expatriates in a small village in Languedoc-Rousillon.
In addition to her comics work, Kominsky-Crumb is also a painter and since moving to France, has focused more on painting and less on producing comics. In February 2007 she released a memoir entitled Need More Love: A Graphic Memoir, a collection of her comics and paintings, along with photographs and autobiographical writings.