An Eightball issue typically contained several short pieces and a chapter of a longer narrative that was later collected and published as a graphic novel, such as Like a Velvet Glove Cast in Iron (1993), Ghost World (1997), David Boring (2000) and Patience (2016).

[citation needed] Clowes and writer Mort Todd co-created a recurring Cracked feature titled The Uggly Family.

One of the most widely acclaimed American alternative comics, it won over two dozen awards, and all of Clowes's Eightball serials have been collected and released as graphic novels.

From #1 to #18, an Eightball issue typically contained short pieces that ranged in genre from comical rant and Freudian analysis to fairy tale and cultural criticism.

These issues also featured a chapter of a serial that Clowes later collected as a graphic novel: Like a Velvet Glove Cast in Iron (1993), Pussey!

The oversized black and white issues #19–21 each contained a single act of Clowes's three-act David Boring, which was released as a graphic novel in 2000.

The next year, Pantheon released Mister Wonderful, a revised and reformatted version of a narrative serialized weekly in 2007 and 2008 in The Sunday New York Times Magazine, a story Clowes described as a "romance.

Ghost World was among the earliest American "literary" comics to be marketed and sold through conventional book stores as a graphic novel.

[18] Reflecting the cartoonist's interest in 1950s and 1960s TV, film, mainstream and underground comics, and Mad magazine, these elements surface in Clowes's 1990s work, especially his graphic novel Like a Velvet Glove Cast in Iron.

[20] For his comics, Clowes has won many Harvey Awards, including Best Writer in 1997 and 2005; Best Series in 1990, 1991, 1992, and 1997; Best Letter in 1991 and 1997; Best Single Issue or Story in 1990, 1991, 1998 and 2005; and Best Cartoonist in 2002.

[22] Clowes received the prestigious Fauve d'Or for his album Monica at the 51e Édition of the "Festival de la BD d'Angoulême" in January 2024.

Based on Clowes's comic of the same name and written with director Terry Zwigoff, the film is set in a nondescript American town and follows the misadventures of two best friends, Enid (Thora Birch) and Rebecca (Scarlett Johansson), who detest most of their high school classmates.

The girls play a prank on a nerdy record collector named Seymour (Steve Buscemi), who quickly becomes Enid's unlikely friend and confidante, as her relationship with Rebecca deteriorates.

Directed by Zwigoff with a script by Clowes, the film follows Jerome (Max Minghella), an art student who dreams of becoming the world's greatest artist.

[29] Clowes also wrote a screenplay based on the true story of three boys who, over the course of seven years, filmed a shot-for-shot remake of Raiders of the Lost Ark.

LaBeouf later issued several apologies on Twitter, writing, "In my excitement and naiveté as an amateur filmmaker, I got lost in the creative process and neglected to follow proper accreditation", and "I deeply regret the manner in which these events have unfolded and want @danielclowes to know that I have a great respect for his work."

[36] In 1993 and 1994, Clowes created artwork for Coca-Cola's Generation X-inspired beverage OK Soda, which was test-marketed in select American cities in 1994 and 1995 and then discontinued.

His art appeared on cans, bottles, twelve-pack cases, posters, vending machines, and other merchandise, along with point-of sale display items.

[37] Clowes has illustrated over 25 LP, EP, and CD covers, including Everything Looks Better in the Dark (1987)[38] by Frank French and Kevn Kinney, Thee Headcoats' Heavens to Murgatroyd, Even!

[39] Clowes drew covers and booklet art for the Criterion Collection's releases of Samuel Fuller's films Shock Corridor and The Naked Kiss (2011).

He drew the key art for Season 4 of the HBO series Silicon Valley (2017)[40] and the cover for Encounter Briefs, a fictional comic book featured in Greg Mottola's film Paul (2011).