Sam Kieth got interested in comics at about the age of nine, when he started collecting and reading comics avidly. He learnt how to draw from his cousins and his sister - one of his cousins made animated cartoons. So he felt like an odd man out for not drawing. He started his professional career when he was seventeen, and first came to attention as the inker of Matt Wagner's 'Mage' in 1983. He sold some work to DC and Marvel, were he got a job working on 'Wolverine' and as an illustrator of several covers.
In 1987, Kieth drew the first five issues of the epic comic series 'The Sandman', written by Neil Gaiman, at DC/Vertigo. He was eventually replaced by his former inker Mike Dringenberg. He collaborated with writer William Messner-Loebs on two volumes of 'Epicurus the Sage' and drew an 'Aliens' miniseries for Dark Horse Comics.
Together with Messner-Loebs, Kieth was the creator of the comic series called 'The Maxx', which was published by Image comics from 1993 until 1998. The success of the series spawned an award-winning cartoon on MTV, trading cards, a toy and even some statues. The story centres around The Maxx, a vagrant that has lost his memory and keeps having dreams of an outback land where he thinks that he might be from. Kieth has subsequently worked as a writer-artist on 'Zero Girl', 'Four Women' and 'Ojo'.