Paul Hornschemeier was born in Cincinnati, Ohio in 1977 and raised in nearby rural Georgetown, Ohio. As a child he liked to draw, dreaming that he might publish his own comic books one day. While majoring in philosophy and psychology at The Ohio State University, Hornschemeier was introduced to the graphic novel Ghost World by Daniel Clowes and began exploring underground and literary comics. He saw that comics could be a venue for exploring issues from his studies and other interests, and within a year he began publishing his own black and white comics, under the banner "Sequential". Those early experimental works have since been compiled by AdHouse Books under the title The Collected Sequential. After graduation from college, Hornschemeier began using colors in his comics. In 2001, after moving to Chicago, he self-published the final issue of "Sequential," and began publishing the full-color comics series "Forlorn Funnies" with (now defunct) Absence of Ink Press. In 2003, Dark Horse Comics published his first graphic novel titled Mother, Come Home.
In 2007 Hornschemeier colored the Marvel mini-series Omega The Unknown.
Hornschemeier also sang and played guitar for the now defunct band Arks.