While early issues of the series tended to focus on humor and social satire, the subject matter shifted over the run to focus more on character-driven dramas. As Clowes's writing began taking on more of a novelistic voice, the series began to focus on longer stories, and the anthology format (wherein Clowes would showcase a variety of artistic and writing styles in works that ranged anywhere from single page joke strips to serialized urban horrors) was seen less and less.
Throughout the series, Clowes makes many allusions to comic book culture, particularly to the Silver Age comics of Marvel and DC. Some of the strips written in homage to this era include "Black Nylon"—about a delusional superhero—and The Death Ray—a stand-alone story about a genuinely superpowered teen who derives his abilities from nicotine. This fascination with the larger comics world is also embodied by one of the series few recurring characters, Dan Pussey. A comic artist who rises to a short-lived fame followed by a long-lived obscurity, Dan's tale is a fictionalized blend of the biographies of several comic artists whose careers saw severe ups and downs, such as Steve Ditko, Rob Liefeld, and the team of Siegel And Shuster.
Tropes found in Eightball include:
- Anthology Comic: The series began as heavily anthologized, with each individual issue packed with comics that ran the gamut from introspective drama to absurdist slapstick. The series veered away from this in latter issues, instead focusing on issue-spanning stories; though the anthology format was still played with, albeit in a more Altmanesque fashion, where many stylistically different vignettes are presented, yet they all interconnect around some central plot or shared setting.
- Cerebus Syndrome: While there the series never shied away from the dark and dramatic, early issues also featured a mix of comedic pieces of all stripes, from satire to absurdist humor. As Clowes became recognized more for his serious-toned work, though, the proliferation of humor pieces decreased. Acknowledged by Clowes when he released Twentieth-Century Eightball, a collection of all the funny bits from the early days.
- It Is Pronounced "Tro-PAY": Dan Pussey is insistent that his last name is pronounced "Poo-SAY." This is not a deterrent to his schoolyard tormentors.
- Most Writers Are Writers: The stories frequently star artists and writers. Enid Coleslaw of Ghost World was an artist, as is Dan Pussey. It's alluded to in David Boring that the title character is a multimedia artist. Two of Ice Haven's main characters are writers. Then there are the numerous short strips about artists and writers (Art School Confidential, Ink Studs, etc.).
- Surrealism: Stock-in-trade for much of the entries in the series. Its first, long-running serial—an urban horror called Like a Velvet Glove Cast in Iron—dealt with dreams and nightmares, and in that effort avoided certainty and clarity, and instead strung together a set of bizarre, often disconnected episodes its protagonist would find himself in.