The first artists for Vampirella were Frank Frazetta (the premiere cover) and Tom Sutton (interior art). Jose Gonzalez became the character's primary artist starting with issue #12. Other artists who would draw Vampirella during her magazine's original run included Gonzalo Mayo, Leopold Sanchez, Esteban Maroto, José Ortiz, Escolano, Rudy Nebres, Ramon Torrents, Pablo Marcos, Jim Janes, John Lakey and Val Lakey.

Backup features appearing in Vampirella included "Doorway to Nightmare ", "Pantha" and "Fleur". Vampirella herself also appeared in a story with fellow Warren characters Pantha and the Rook in Eerie #94-95, and with most of the Warren characters in a company crossover special in Eerie #130. The final issue of the original Vampirella was cover-dated March 1983.

Upon Warren's bankruptcy shortly afterward, Harris Publications acquired the company assets at auction in August 1983, although legal murkiness and a 1998 lawsuit by Warren publisher James Warren resulted in his reacquisition of the rights to sister publication Vampire Tales. Harris Comics published Vampirella stories in various series and miniseries from 1991 to 2007. Harris also published Vampirella #113, a one-issue continuation of the original series, containing solely reprinted stories, in 1988.

At the Fangoria Weekend of Horrors convention in January 2007, Scott Licina, editor-in-chief of Fangoria Comics, announced his company had acquired the character from Harris. However, on April 30, 2007, Harris editor Bon Alimagno denied there had been such an arrangement in place and that Fangoria's claim was "not factual". Harris subsequently launched the title Vampirella Quarterly.