Adams attended the School of Industrial Art high school in Manhattan. After graduation in 1959, he unsuccessfully attempted to find freelance work at DC Comics, and turned then to Archie Comics, where he wanted to work on the publisher's fledgling superhero line, edited by Joe Simon. At the suggestion of staffers, Adams drew "three or four pages of [the superhero] the Fly", but did not receive encouragement from Simon. Sympathetic staffers nonetheless asked Adams to draw samples for the Archie teen-humor comics themselves. While he did so, Adams said in a 2000s interview, he unknowingly broke into comics:

That panel ran in Adventures of the Fly #4 (Jan. 1960). Afterward, Adams began writing, penciling, inking, and lettering humorous full-page and half-page gag fillers for Archie's Joke Book Magazine. In a 1976 interview, he recalled earning "[a]bout $16.00 per half page and $32.00 for a full page. That may not seem like a great deal of money, but at the time it meant a great deal to myself as well as my mothers ... as we were not in a wealthy state. It was manna from heaven, so to speak". A recommendation led him to artist Howard Nostrand, who was beginning the Bat Masterson syndicated newspaper comic strip, and worked as Nostrand's assistant for three months, primarily drawing backgrounds at what Adams recalled as $9 a week and "a great experience".

Having "not left Archie Comics under the best of circumstances", Adams turned to commercial art for the advertising industry. After a rocky start freelancing, he began landing regular work at the Johnstone and Cushing agency, which specialized in comic-book styled advertising. Helped by artist Elmer Wexler, who critiqued the young Adams' samples, Adams brought his portfolio to the agency, which initially "didn't believe I had done those particular samples since they looked so much like Elmer Wexler's work. But they gave me a chance and ... I stayed there for about a year".

Ben Casey

In 1962, Adams began his comics career in earnest at the NEA newspaper syndicated. At the recommendation of Adams's Johnstone and Cushing friend and stablemate Tom Scheuer, writer Jerry Caplin, a.k.a. Jerry Capp, brother of Li'l Abner creator Al Capp, invited Adams to draw samples for Capp's proposed Ben Casey comic strip, based on the popular television medical-drama series. On the strength of his samples and of his "Chip Martin, College Reporter" AT&T advertising comic-strip pages in Boys' Life magazine, and of his similar Goodyear Tire ads, Adams landed the assignment. The first daily strip, which carried Adams' signature, appeared November 26, 1962; a color Sunday strip was added September 20, 1964.

Comics historian Maurice Horn said the strip "did not shrink from tackling controversial problems, such as heroin addiction, illegitimate pregnancy, and attempted suicide. These were usually treated in soap opera fashion ... but there was also a touch of toughness to the proceedings, well rendered by Adams in a forceful, direct style that exuded realism and tension and accorded well with the overall tone of the strip".

In addition to Capp, Jerry Brondfield also wrote for the strip, with Adams stepping in occasionally.

The ABC series, which ran five seasons, ended March 21, 1966, with the final comic strip appearing Sunday, July 31, 1966. Despite the end of the series, Adams has said the strip, which he claimed at different points to have appeared in 365 newspapers, 265 newspapers, and 165 newspapers, ended "for no other reason that it was an unhappy situation":

Adams' goal at this point was to be a commercial illustrator. While drawing Ben Casey, he had continued to do storyboards and other work for ad agencies, and said in 1976 that after leaving the strip he had shopped around a portfolio for agencies and for men's magazines, "but my material was a little too realistic and not exactly right for most. I left my portolio in an an advertising agency promising they were going to hold on to it. In the meantime I needed to make some money ... and I thought, 'Why don't I do some comics?'" In a 2000s interview, he remembered the events slightly differently, saying "I took [my portfolio] to various advertising people. I left it at one place overnight and when I came back to get it the next morning it was gone. So six months worth of work down the drain...."

He worked as a ghost artist for a few weeks in 1966 on the comic strip Peter Scratch (1965—1967), a hardboiled detective serial created by writer Elliot Caplin and artist Lou Fine. Comics historians also credit Adams with ghosting two weeks of dailies for Stan Drake's The Heart of Juliet Jones, but are uncertain on dates; some sources give 1966, another 1968, and Adams himself 1963. As well, Adams drew 18 sample dailies (three weeks' continuity) of a proposed dramatic serial, Tangent, about construction engineer Barnaby Peake, his college-student brother Jeff, and their teenaged sibling Chad, in 1965, but it was not syndicated. Adams later said that writer Elliot Caplin, brother of Al Capp and Jerry Capp, offered Adams the job of drawing a comic strip based on author Robin Moore's The Green Berets, but that Adams, who opposed the war, suggested longtime DC Comics war-comics artist Joe Kubert, who landed that assignment.

Silver Age splash

Turning to comic books, Adams found work at Warren Publishing's black-and-white horror-comics magazines, under editor Archie Goodwin. Adams debuted there as penciler and inker of writer Goodwin's eight-page anthological story "Curse of the Vampire" in Creepy #14 (April 1967). He and Goodwin quickly collaborated on two more stories, in Eerie #9 (May 1967) and Creepy #15 (June 1967), and Adams as well reapproached DC Comics.

With DC war comics stalwart Joe Kubert now concentrating on the comic strip The Green Berets, Adams saw an opening:

Adams made his DC debut as penciler-inker of the 8½-page story "It's My Turn to Die", written by Howard Liss, in the anthology series Our Army at War #182 (July 1967). He did a smattering of additional horror and war stories, respectively, for the two publishers, and then, after being turned down by DC's Batman editor Julius Schwartz, approached fellow DC editor Murray Boltinoff in the hopes of drawing for Boltinoff's Batman team-up title The Brave and the Bold. Boltinoff instead assigned him the cover of The Adventures of Bob Hope #106 (Sept. 1967) and its 23-page story "Badgers [sic] Baby Brother ... Beastley", written by Arnold Drake. It became the first of a slew of stories and covers Adams would draw for that series and The Adventures of Jerry Lewis, two licensed titles starring fictional versions of the TV, film and nightclub comics.

During this period near the end of the industry revival historians call the Silver Age of comic books, Adams was soon assigned his first superhero covers, illustrating that of the Superman flagship Action Comics #356 (Nov. 1967) and the same month's Superman's Girl Friend, Lois Lane #79 (Nov. 1967), featuring Superman and a mysterious new costumed character, Titanman. Also that month, Adams drew his first superhero story, teaming with writer Gardner Fox on the lighthearted backup feature "The Elongated Man" in Detective Comics #369, the flagship Batman title. Shortly afterward, he drew Batman himself, along with the supernatural superhero the Spectre, on the cover of The Brave and the Bold #75 (Jan. 1968) ... the first published instance of Adams' work on what would become two of his signature comics characters.

Another, his breakout character, was the supernatural hero Deadman, who had debuted in DC's Strange Adventures #205 (Nov. 1967). Adams succeeded co-creator artist Carmine Infantino with the following issue's 17-page story "An Eye for an Eye", written by Arnold Drake, with George Roussos inking Adams' pencils. Adams went on to draw both the covers and stories for issues 207-216 (Dec. 1967 - Feb. 1969), and taking over the scripting with #212 (June 1968). The series became a fan sensation, winning many awards and being almost immediately inducted into the Alley Award Hall of Fame, with Adams himself receiving a special award "for the new perspective and dynamic vibrance he has brought to the field of comic art".

Adams concurrently drew covers and stories for The Spectre #2-5 (Feb.-Aug. 1968), also writing the latter two issues, and became DC's primary cover artist well into the 1970s. Adams recalled that Infantino "was appointed art director, and decided I was going to be his spark plug. I also thought it was a good idea, and was promised a number of things which were never fulfilled. But I thought it would be an adventure anyway, so I knuckled down to things like "Deadman", The Spectre and whatever odd things would come my way. I was also doing large amounts of covers".

Adams' art style, honed in advertising and in the photorealistic school of dramatic-serial comics strips, marked a signal change from most comics art to that time. Comics writer and columnist Steve Grant wrote in 2009 that,

First Marvel Comics work

While continuing to freelance for DC, Adams in 1969 also began freelancing for Marvel Comics, where he penciled several issues of the mutant-superhero team title X-Men and one story for a horror anthology title. Such freelancing across the two leading companies was rare at the time; most DC creators who did so worked pseudonymously. Adams recalled in 1976:

He teamed with writer Roy Thomas on X-Men, then on the verge of cancellation, starting with issue #56 (May 1969). Adams penciled and colored, paired for the first time with inker Tom Palmer, with whom he would collaborate on several acclaimed Marvel comics; the duo's work here netted them 1969 Alley Awards for Best Pencil Artist and Best Inking Artist, respectively. (Thomas won that year for Best Writer.) Though the team failed to save the title, which ended its initial run with #66 (Dec. 1969), the collaboration here and on the "Kree-Skrull War" arc of The Avengers #93-97 (Nov. 1971 - May 1972) produced what comics historians regard as some of Marvel's creative highlights of the era. Adams also wrote and penciled the horror story "One Hungers" in Tower of Shadows #2 (Dec. 1969), and co-wrote with Thomas, but did not draw, another in Chamber of Darkness #2 (Dec. 1969).

Green Lantern/Green Arrow and "relevant comics"

Continuing to work for DC Comics during this sojourn, while also contributing the occasional story to Warren Publishing's black-and-white horror-comics magazines (including the Don Glut-scripted "Goddess from the Sea" in Vampirella #1, Sept. 1969), Adams had his first collaboration on Batman with writer Dennis O'Neil. The duo would later revitalize the character with a series of noteworthy stories reestablishing Batman's dark, brooding nature and taking the books away from the campy look and feel of the 1966-68 ABC TV series. For now, however, they would do only two stories, "The Secret of the Waiting Graves" in Detective Comics #395 (Jan. 1970) and "Paint a Picture of Peril" in issue #397 (March 1970), with a short Batman backup story, written by Mike Friedrich, coming in-between, in Batman #219 (Feb. 1970). Batman's enduring makeover would come later, after Adams and O'Neil's celebrated and, for the time, controversial revamping of the longstanding DC characters Green Lantern and Green Arrow.

Rechristening Green Lantern vol. 2 as Green Lantern/Green Arrow with issue #76 (April 1970), O'Neil and Adams teamed these two very different superheroes in a long story arc in which the characters undertook a social-commentary journey across America. A major exemplar of what the industry and the public at the time called "relevant comics", the landmark run began with the 23-page story "No Evil Shall Escape My Sight" and continued to " ...And through Him Save a World" in the series' finale, #89 (May 1972). Wrote historian Ron Goulart,

Movie and theater work

Adams' pencil drawings on his later Batman stories were frequently inked by Dick Giordano, with whom Adams formed Continuity Associates, a company that primarily supplied storyboards for motion pictures. In the early 1970s, Adams was the art director, costume designer, as well as the poster/Playbill illustrator for Warp!, a science fiction stage play by director Stuart Gordon and playwright Lenny Kleinfeld under the pseudonym Bury St. Edmund that had had some cult success in Chicago, and which played on Broadway from Feb. 14-18, 1973, at the original Ambassador Theatre.

Creator's rights

During the 1970s, Adams was politically active in the industry, and attempted to unionize its creative community. His efforts, along with precedents set by Atlas/Seaboard Comics' creator-friendly policies and other factors, helped lead to the modern industry's standard practice of returning original artwork to the artist, who can earn additional income from art sales to collectors. He won his battle in 1987, when Marvel returned original artwork to him and industry legend Jack Kirby, among others. Adams notably and vocally helped lead the lobbying efforts that resulted in Superman creators Jerry Siegel and Joe Shuster receiving decades-overdue credit and some financial remuneration from DC.

Inker Bob McLeod recalled in the 2000s the unique place Adams held in the industry when McLeod broke into comics in 1973:

In 1978, Adams helped form the Comics Creators Guild, which over three dozen comic-book writers and artists joined.