Howie Cohen, an advertising copywriter, often said he was congenitally familiar with indigestion. So perhaps it was only natural that in the 1970s, he, along with an ad agency colleague, would conjure up a catchy slogan that would not only sell more Alka-Seltzer but also become an American pop culture punchline: “I can’t believe I ate the whole thing.”

That bedside lament, spoken by the comedian and dialectician Milt Moss — he actually said that thing on camera — vaulted from a 30-second TV commercial to sweatshirts, supermarket windows and even church marquees.

It proved even more popular than “Try it, you’ll like it,” the first catchphrase for Alka-Seltzer that Mr. Cohen coined with his business partner, Bob Pasqualina, an art director at the Manhattan agency Wells Rich Greene.

Mr. Cohen, who helped popularize products and companies like Petco (“Where the pets go”) and the fast-food chain Jack in the Box (exploding its clown mascot in a TV commercial in announcing a new, more sophisticated menu), died on March 2 at his home in Los Angeles. He was 81.

His death, which wasn’t widely reported at the time, was announced on Facebook by his brother, Jerry, who said the cause was cancer.

Alka-Seltzer’s creative advertising had already found success in the 1950s and ’60s. It had introduced its mascot Speedy and its “plop, plop, fizz, fizz” jingle. It had brought “tummies” to television commercials. And it had played on cultural stereotypes (“that’s a spicy meatball”), offending some viewers. But by the early 1970s, sales were lagging.

Mr. Cohen and Mr. Pasqualina, who had recently joined Wells Rich Greene, were tasked with creating an ad campaign that would run until the agency could come up with a long-term strategy to make Alka-Seltzer a household name again.

Mr. Cohen recalled in a 2019 memoir that those two popular ads the partners came up with, both in 1972, were inspired by his upbringing in the Pelham Parkway neighborhood of the East Bronx.

The “try it” tag line had its roots, he wrote, in his mother’s dinnertime plea that he eat the liver and onions that regularly congealed untouched on his plate.

“We only had 30 seconds, so we couldn’t get too complicated,” Mr. Cohen told The New York Times in 1972. “One of us came up with ‘Try it, you’ll like it.’ We said it over and over again, because we couldn’t think of another line, and the repetition became the thing.”

In the ad, Jack Aaron, a stage actor who had appeared in commercials, plays a man sitting in a restaurant recounting a meal he once had — an indigestible one, it turned out — at the encouragement of a waiter, who kept telling him, “Try it, you’ll like it.”

“I used to work part time as a waiter,” Mr. Aaron told The Times in 1972. “Now I eat at Sardi’s, and the waiters all say, ‘Try it, you’ll like it.’”

If “try it” was inspired by Mr. Cohen’s abstinence, the “whole thing” line resulted from his overindulgence. He, Mr. Pasqualina and a production crew were in London gorging on an Italian dinner hosted by the director Milos Forman, who had filmed a commercial that the two admen had created for Diet Rite Cola.

“I’m a nice Jewish kid from the Bronx, so I ate everything until I couldn’t fit one more thing in my body,” Mr. Cohen would often recall. “I leaned back in my chair and said, ‘I can’t believe I ate the whole thing.’ And my wife said, ‘There’s your next Alka-Seltzer commercial.’”

In the commercial, a woman, trying to fall back to sleep, urges her pajama-clad husband, who is sitting groaning on the edge of their bed, to take two Alka-Seltzer tablets to settle his stomach after overindulging. He repeats the “whole thing” line over and over.

Both ads are enshrined in the advertising industry’s Clio Awards Hall of Fame.

A marketing survey found that about 85 percent of Americans could identify Alka-Seltzer through the “whole thing” slogan, which would later be immortalized in the game Trivial Pursuit and on the TV animated series “The Simpsons.”

“They say the best lines come from the heart,” Mr. Cohen wrote in his book, “I Can’t Believe I Lived the Whole Thing: A Memoir From the Golden Age of Advertising.” “‘I can’t believe I ate the whole thing’ came from my stomach.’”

Mary Wells Lawrence, one of the founders of Wells Rich Greene and Mr. Cohen’s mentor, described Mr. Cohen and Mr. Pasqualina as “two of the most talented people we ever had.”

Ms. Wells Lawrence, who died in May, wrote in her own memoir that earlier Alka-Seltzer ads had grabbed attention and entertained, but that “they were not as believable, as earnestly sincere and therefore not as persuasive as Howie and Bob’s sweet, funny commercials — especially ‘I ate the whole thing.’”

Howard Stephen Cohen was born on Sept. 25, 1942, in the Bronx to Samuel and Jeannette Cohen. The elder Mr. Cohen owned a steel fabrication company that he had inherited from his father.

Howie Cohen wrote in his memoir that he grew up in a one-bedroom apartment adjacent to an elevated train. When he was 13, he was given a tape recorder as a bar mitzvah gift and began producing commercials. After graduating from New Rochelle High School in Westchester County, he attended the University of Miami and earned a bachelor’s degree in business from New York University.

Destined to inherit his father’s company but eager not to, he applied to ad agencies and in 1965 landed a job as a copy trainee on the Volkswagen account at Doyle Dane Bernbach.

He joined Wells Rich Greene in 1967; left to start his own firm with Mr. Pasqualina; returned to Wells Rich Greene as a creative director; became the president of its Los Angeles office; and founded another agency with the adman Mark Johnson, which he sold in 1997 to the Phelps Group. He remained as partner and chief creative officer until he retired in 2017. He also wrote a blog called Mad Mensch.

In addition to his brother, his survivors include his wife, Carol (Trifari) Cohen, whom he married in 1972; two children, Jonathan and Johanna; a stepdaughter, Cristina; and a granddaughter.

In 2012, Mr. Cohen was asked by Google to reimagine the “I can’t believe I ate the whole thing” ad for a 21st-century digital version.

“I look at the internet tools and technologies that we have and see exciting new ways to express an idea,” he told The Los Angeles Times. “But emotions will always trump algorithms. Advertising is about connecting in a human way.”