Chaykin's influences include his one-time employer and mentor, Gil Kane, and the mid-20th century illustrators Robert Fawcett and Al Parker.

[3] He said in 2000 he was raised on welfare after his parents separated and that his absent biological father eventually was declared dead, although Chaykin, as an adult, located him alive.

[3] Chaykin said that after high school, "I hitchhiked around the country" before becoming, at 19, a "gofer" for the New York City–based comic book artist Gil Kane,[5] whom he would name as his greatest influence.

[3] Leaving Kane, he began working as an assistant to comics artist Wally Wood[8] in the studio he shared with Syd Shores and Jack Abel in Valley Stream, Long Island.

[10]The "one-page filler", titled "Strange Neighbor", was inventoried and eventually published in the Boltinoff-edited Secrets of Sinister House #17 (May 1974).

[11] At one point Chaykin lived in the same Queens apartment building as artists Allen Milgrom, Walter Simonson, and Bernie Wrightson.

'"[12] Chaykin's first major work was for DC Comics drawing the 23-page "The Price of Pain Ease"—writer Denny O'Neil's adaptation of author Fritz Leiber's characters Fafhrd and the Gray Mouser—in Sword of Sorcery #1 (March 1973).

Chaykin drew the character Ironwolf in the science fiction anthology title Weird Worlds[14] for DC, and did the pencils and ink for a 12-page Batman story written by Archie Goodwin and published in Detective Comics #441 in 1974.

"[15] Moving to Marvel Comics, he began work as co-artist with Neal Adams on the first Killraven story, seen in Amazing Adventures #18 in 1973.

In 1976, Chaykin landed the job of drawing the Marvel Comics adaptation of the first Star Wars film, written by Roy Thomas.

In late 1978,[20] Chaykin, Walt Simonson, Val Mayerik, and Jim Starlin formed Upstart Associates, a shared studio space on West 29th Street in New York City.

Chaykin collaborated on two original graphic novels—The Swords of Heaven, the Flowers of Hell with writer Michael Moorcock, and Empire with Samuel R. Delany—and found time to move into film design with work on the movie version of Heavy Metal.

[25] He went back to Cody Starbuck with a story in Heavy Metal between May and September 1981, in the same painted art style he'd used for the Moorcock graphic novel.

In June 1980, a story that he collaborated on with Samuel R. Delany, called "Seven Moons' Light Casts Complex Shadows" was published in Marvel's Epic Illustrated #2.

Chaykin made wide use of Craftint Duoshade illustration boards, which in the period before computers allowed him to add a shaded texture to the finished art.

In 1987, a four-issue run was released, then the title was cancelled and relaunched as Howard Chaykin's American Flagg!, which ran 12 issues.

"[33] Before returning to American Flagg!, Chaykin revamped another DC Comics character with Blackhawk, a three-issue miniseries about a team of heroic aviators, set in the 1930s.

[34] In 1988, Chaykin created perhaps his most controversial[35] title: Black Kiss, a 12-issue series published by Vortex Comics that contained his most explicit depictions of sex and violence, with a story of sex-obsessed vampires in Hollywood.

Later, Chaykin collaborated twice with artist Mike Mignola: In 1990–1991, they produced the Fafhrd and the Gray Mouser miniseries for Epic Comics with co-writer John Francis Moore and inker Al Williamson.

In 1996, DC's Helix imprint published Cyberella, a cyberpunk dystopia written by Chaykin and drawn by Don Cameron.

He was executive script consultant for the 1990–1991 The Flash television series on CBS,[39] and later worked on action-adventure programs such as Viper, Earth: Final Conflict and Mutant X.

Near the end of the decade, Chaykin returned to comics and co-wrote with David Tischman the three-issue miniseries Pulp Fantastic for the Vertigo imprint of DC, with art by Rick Burchett.

[45] In 2006, he began working on his first superhero title for DC Comics, pencilling Hawkgirl, with Walter Simonson writing, starting with issue #50.

Also in 2006, DC Comics published a two-page Black Canary origin story drawn by Chaykin for the series 52.

The two-issue series, written and drawn by Chaykin, revolves around the Green Lantern Corps' role in an interstellar war.

Chaykin illustrated the 2008 Marvel MAX comic War Is Hell: The First Flight of the Phantom Eagle, scripted by Garth Ennis.

[47] Marvel in June 2010 published a Rawhide Kid miniseries drawn by Chaykin and written by Ron Zimmerman.

[48] Chaykin helmed a reboot of the science-fiction character Buck Rogers beginning in August 2013, again in the capacity of both artist and writer.

[50] In April 2022, Chaykin was reported among the more than three dozen comics creators who contributed to Operation USA's benefit anthology book, Comics for Ukraine: Sunflower Seeds, a project spearheaded by IDW Publishing Special Projects Editor Scott Dunbier, whose profits would be donated to relief efforts for Ukrainian refugees resulting from the February 2022 Russian invasion of Ukraine.