Wrightson received training in art from watching Jon Gnagy on television, reading comics, particularly those of EC, as well as through a correspondence course from the Famous Artists School. His early (and lasting) artistic influences were Frank Frazetta and Graham Ingels. He published a piece of fan art, containing a headstone bearing the inscription “Berni Wrightson, Dec. 15, 1965”, on page 33 of Warren Publishing’s Creepy #9 (cover-dated June 1966).
In 1966, Wrightson began working for The Baltimore Sun newspaper as an illustrator. The following year, after meeting artist Frank Frazetta at a comic-book convention in New York City, he was inspired to produce his own stories. In 1968, he showed copies of his sequential art to DC Comics editor Dick Giordano and was given a freelance assignment. Wrightson began spelling his name “Berni” in his professional work to distinguish himself from an Olympic diver named Bernie Wrightson, but later restored the final “e” to his name.
In 1968 he drew his first professional comic book story, “The Man Who Murdered Himself”, which appeared in House of Mystery No. 179 (March–April 1969). He continued to work on a variety of mystery and anthology titles for both DC and, a few years later, its principal rival, Marvel Comics. It was for Marvel’s Chamber of Darkness and Tower of Shadows titles where he was first encouraged to slightly simplify his intricate pen-and-ink drawing, and where his lush brushwork, a hallmark of his comics inking in the 1970s, was first evidenced.
With writer Len Wein, Wrightson co-created the muck creature Swamp Thing in House of Secrets No. 92 (July 1971) in a standalone horror story set in the Victorian era. Wein later recounted how Wrightson became involved with the story: “Bernie Wrightson had just broken up with a girlfriend, and we were sitting in my car just talking about life – all the important things to do when you’re 19 and 20 years old. [Laughs] And I said, ‘You know, I just wrote a story that actually kind of feels like the way you feel now.’ I told him about Swamp Thing, and he said, ‘I gotta draw that.'”
In summer 1972 he published Badtime Stories, a horror/science fiction comics anthology featuring his own scripts and artwork (from 1970–71), each story being drawn in a different medium (ink wash, tonal pencil drawings, duoshade paper, screen tones, e.g., along with traditional pen-and-ink and brushwork).
He and writer Marv Wolfman co-created Destiny in Weird Mystery Tales No. 1 (July–Aug. 1972), a character which would later be used in the work of Neil Gaiman.
In the fall of 1972 the Swamp Thing returned in his own series, set in the contemporary world and in the general DC continuity. Wrightson drew the first ten issues of the series. Abigail Arcane, a major supporting character in the Swamp Thing mythos was introduced in issue No. 3 (Feb.-March 1973).
Wrightson had originally been asked by DC to handle the art for its revival of The Shadow, but he left the project early on when he realized he could not produce the necessary minimum number of pages on time, along with his work on Swamp Thing. Michael Kaluta illustrated the series, but Wrightson did contribute much to the third issue in both pencils and inks, as well as inking the splash page of issue four.
In January 1974, he left DC to work at Warren Publishing, for whose black-and-white horror-comics magazines he produced a series of original work as well as short story adaptations. As with BadTime Stories, Wrightson experimented with different media in these black-and-white tales: Edgar Allan Poe’s “The Black Cat” featured intricate pen-and-ink work which stood in direct contrast with his brush-dominated Swamp Thing panels. “Jenifer”, scripted by Bruce Jones, was atmospherically rendered with gray markers. “The Pepper Lake Monster” was a synthesis of brush and pen-and-ink, whereas H.P. Lovecraft’s “Cool Air” was a foray into duotone paper. “Nightfall” was an exercise in ink wash and a subtle “Little Nemo in Slumberland” satire, and “The Muck Monster” a sequential art precursor to Wrightson’s Frankenstein, with the Franklin Booth-inspired pen-and-ink style in evidence. “Clarice” was also drawn in pen, brush, and ink, and with ink wash.
In 1975, Wrightson joined with fellow artists Jeff Jones, Michael Kaluta, and Barry Windsor-Smith to form The Studio, a shared loft in Manhattan where the group would pursue creative products outside the constraints of comic book commercialism. Though he continued to produce sequential art, Wrightson at this time began producing artwork for numerous posters, prints, calendars, and even a highly detailed coloring book. He also drew sporadic comics stories and single illustrations for National Lampoon magazine from 1973 to 1983.
Wrightson spent seven years drawing approximately 50 detailed pen-and-ink illustrations to accompany an edition of Mary Shelley’s novel Frankenstein.