Skal studied journalism at Ohio University, where he worked as a film critic and assistant editor for the college's newspaper. He graduated with a bachelor's degree in 1974. After graduation, he interned with the National Endowment for the Arts and became the publicity director for the Hartford Stage Company. He later held positions with the American Conservatory Theater in San Francisco and the Theatre Communications Group of New York. During the 1980s, Skal completed three science fiction novels: Scavengers (1980), When We Were Good (1981), and Antibodies (1988).

Skal's first nonfiction work was 1990's Hollywood Gothic: The Tangled Web of Dracula from Novel to Stage to Screen. This book discusses the various adaptations of Bram Stoker's 1897 novel Dracula, and the role of the vampire archetype in popular culture. A large portion of the book describes the efforts of Stoker's widow Florence to protect the rights to her husband's work. The book also contains the first in-depth study of a Spanish-language Dracula film produced in 1931. Kathleen Quinn of the New York Times praised Hollywood Gothic, writing, "Skal tracks Transylvania's most popular vampire with dry wit and the skills of a fine detective." Kenneth Turan of the Los Angeles Times called it "witty and comprehensive", and quipped that it was "something to gnaw on long after those trick-or-treaters are gone". Writing in 2004, David Colton of USA Today noted that the book had "become one of the field's essential reads" and had "[raised] the standards for horror researchers".

In 1993, Skal released his second non-fiction book, titled The Monster Show: A Cultural History of Horror. In this book, Skal analyzes the history of horror films, drawing parallels between those films and the cultural crises of their times, such as World War I, World War II, the thalidomide controversies, and the AIDS epidemic. M.L. Lyke of the Seattle Post-Intelligencer called The Monster Show "the perfect intellectual primer for a Halloween weekend". Stefan Dziemianowicz of the Washington Post argued that some of Skal's arguments were "pretty far-fetched", but added that, as a whole, the book "offers persuasive evidence that in order to understand a culture, you must know what it fears".

Skal collaborated with Elias Savada to produce 1995's Dark Carnival: The Secret World of Tod Browning, Hollywood's Master of the Macabre. Dark Carnival was the first book-length biography of Tod Browning, best known for directing Freaks and the 1931 version of Dracula. Writing in the Journal of Popular Film and Television, Martin F. Norden described it as "a compelling, in-depth examination of one of America's first cult film directors". Steven E. Alford of the Houston Chronicle remarked, "Dark Carnival succeeds in resurrecting the reputation of one of Hollywood's long-buried eccentrics."

Skal's other major publications include V Is for Vampire: The A to Z Guide to Everything Undead (1996), Screams of Reason: Mad Science and Modern Culture (1998), A Cultural History of Halloween (2002), and Claude Rains: An Actor's Voice (2008). Skal also co-edited the 1997 Norton Critical Edition of Bram Stoker's Dracula and compiled the 2001 anthology Vampires: Encounters with the Undead.

Skal has made several appearances in television specials, such as The 100 Scariest Movie Moments and The Perfect Scary Movie. He has produced DVD supplemental documentaries and/or audio commentaries for a number of films, including Dracula (1931), Frankenstein (1931), The Invisible Man (1932), Freaks (1932), The Mummy (1933), Bride of Frankenstein (1935), The Wolfman (1942), Abbott and Costello Meet Frankenstein (1948), Creature from the Black Lagoon (1954), and Gods and Monsters (1998).