Jaffee died Monday in Manhattan from multiple organ failure, according to his granddaughter, Fani Thomson. He had retired at the age of 99.

Mad magazine, with its wry, sometimes pointed send-ups of politics and culture, was essential reading for teens and preteens during the baby-boom era and inspiration for countless future comedians. Few of the magazine’s self-billed “Usual Gang of Idiots” contributed as much — and as dependably — as the impish, bearded cartoonist. For decades, virtually every issue featured new material by Jaffee. His collected “Fold-Ins,” taking on everyone in his unmistakably broad visual style from the Beatles to TMZ, was enough for a four-volume box set published in 2011.

Readers savored his Fold-Ins like dessert, turning to them on the inside back cover after looking through such other favorites as Antonio Prohías’ “Spy vs. Spy” and Dave Berg’s “The Lighter Side.” The premise, originally a spoof of the old Sports Illustrated and Playboy magazine foldouts, was that you started with a full-page drawing and question on top, folded two designated points toward the middle and produced a new and surprising image, along with the answer.

The Fold-In was supposed to be a onetime gag, tried out in 1964 when Jaffee satirized the biggest celebrity news of the time: Elizabeth Taylor dumping her husband, Eddie Fisher, in favor of “Cleopatra” co-star Richard Burton. Jaffee first showed Taylor and Burton arm in arm on one side of the picture, and on the opposite side a young, handsome man being held back by a policeman.

Fold the picture in and Taylor and the young man are kissing.

The idea was so popular that Mad editor Al Feldstein wanted a follow-up. Jaffee devised a picture of 1964 GOP presidential contenders Nelson Rockefeller and Barry Goldwater that, when collapsed, became an image of Richard Nixon.

“That one really set the tone for what the cleverness of the Fold-Ins has to be,” Jaffee told the Boston Phoenix in 2010. “It couldn’t just be bringing someone from the left to kiss someone on the right.”

Jaffee was also known for “Snappy Answers to Stupid Questions,” which delivered exactly what the title promised. A comic from 1980 showed a man on a fishing boat with a noticeably bent reel. “Are you going to reel in the fish?” his wife asks. “No,” he says, “I’m going to jump into the water and marry the gorgeous thing.”

Jaffee didn’t just satirize the culture; he helped change it. His parodies of advertisements included such future real-life products as automatic redialing for a telephone, a computer spell checker and graffiti-proof surfaces. He also anticipated peelable stamps, multiblade razors and self-extinguishing cigarettes.

Jaffee’s admirers ranged from Charles M. Schulz of “Peanuts” fame and “Far Side” creator Gary Larson to Jon Stewart and Stephen Colbert, who marked Jaffee’s 85th birthday by featuring a Fold-In cake on “The Colbert Report.” When Stewart and “The Daily Show” writers put together the best-selling “America (The Book),” they asked Jaffee to contribute a Fold-In.

“When I was done, I called up the producer who’d contacted me, and I said, ‘I’ve finished the Fold-In, where shall I send it?’ And he said — and this was a great compliment — ‘Oh, please Mr. Jaffee, could you deliver it in person? The whole crew wants to meet you,'” he told The Boston Phoenix.

Jaffee received numerous awards, and in 2013 was inducted into the Will Eisner Hall of Fame, the ceremony taking place at San Diego Comic-Con International. In 2010, he contributed illustrations to Mary-Lou Weisman’s “Al Jaffee’s Mad Life: A Biography.” The following year, Chronicle Books published “The MAD Fold-In Collection: 1964-2010.”

Art was the saving presence of his childhood, which left him with permanent distrust of adults and authority. He was born in Savannah, Georgia, but for years was torn between the U.S., where his father (a department store manager) preferred to live, and Lithuania, where his mother (a religious Jew) longed to return. In Lithuania, Jaffee endured poverty and bullying, but also developed his craft. With paper scarce and no school to attend, he learned to read and write through the comic strips mailed by his father.

By his teens, he was settled in New York City and so obviously gifted that he was accepted into the High School of Music & Art. His schoolmates included Will Elder, a future Mad illustrator, and Harvey Kurtzmann, a future Mad editor. (His mother, meanwhile, remained in Lithuania and was apparently killed during the war).

He had a long career before Mad. He drew for Timely Comics, which became Marvel Comics; and for several years sketched the “Tall Tales” panel for the New York Herald Tribune. Jaffee first contributed to Mad in the mid-1950s. He left when Kurtzmann quit the magazine, but came back in 1964.

Mad lost much of its readership and edge after the 1970s, and Jaffee outlived virtually all of the magazine’s stars. But he rarely lacked for ideas even as his method, drawing by hand, remained mostly unchanged in the digital era.

“I’m so used to being involved in drawing and knowing so many people that do it, that I don’t see the magic of it,” Jaffee told the publication Graphic NYC in 2009. “If you reflect and think about it, I’m sitting down and suddenly there’s a whole big illustration of people that appears. I’m astounded when I see magicians work; even though I know they’re all tricks. You can imagine what someone thinks when they see someone drawing freehand and it’s not a trick. It’s very impressive.”