Early issues of Eightball feature a mixture of very short, often crudely humorous comics ("Zubrick and Pogeybait", "The Sensual Santa"), topical rants and satires ("Art School Confidential", "On Sports"), longer, more reflective self-contained stories ("Caricature", "Immortal Invisible"), and serialized works.

The first extended story serialized in Eightball was Like a Velvet Glove Cast in Iron, which ran in issues #1–10.

Additionally, the 2006 Clowes/Zwigoff film Art School Confidential was loosely based on a short story of the same name which appeared in Eightball #7.

The comic generated controversy when a high school teacher in Guilford, Connecticut gave Eightball #22 (Ice Haven) to a student as a make-up summer reading assignment.

[1] The Guilford school district and principal were criticized for getting police involved and trying the issue in a "kangaroo court".