Flora had a cartoonish style that, in its earliest (1940s and 1950s) incarnations, betrayed a diabolic humor and uninhibited sense of outrageousness. Despite a later reputation for "cuddly" kiddie lit and family-friendly illustrations for mainstream magazines, Flora's fine art—both early and late—was by turns bizarre, playful, comic, erotic and/or macabre. It could, on occasion, shock or offend.

His style evolved radically over the decades; comparing his sharp, edgy commercial work of the 1940s to his middlebrow buffoonery of the 1970s sometimes leaves the impression they were done by two different artists who happened to share the same name (he was always credited as James Flora). It seems that the more popular Flora became, the less "threatening" his art appeared. This is certainly true of his commercial work, which softened and became more generic in the 1960s and 1970s.

His private fine art, however, often served as an outlet for the artist's inner demons, as Flora dotted many works with images of violence and sexual excess. (The cover of The Curiously Sinister Art of Jim Flora is adorned with figures from his 1940s absurdist burlesque painting, The Rape of the Stationmaster's Daughter.) Many of his smaller temperas and pen and ink sketches, particularly from the 1940s through the 1960s, featured clusters of unrelated images interlocking like rune-shaped brickwork, every square inch of surface crammed with bizarre figures, some disturbing, some nonsensical, all intriguing. As Flora once explained, "I could never stand a static space." Music was one of Flora's muses, and his montages radiate overtones of improvisation—a one-man band jamming on a canvas. His biographer, Irwin Chusid, said that Flora "crafted rhythmic design in unfathomable meters."

He also established a reputation in the 1980s for large canvases with nautical themes, particularly ocean liners and cruise ships—the decks sometimes populated with tiny figures engaged in pornographic behavior. "When he was in his ship period," said his daughter Roussie, "he painted lots of naughty little scenes going on inside. He would have exhibitions, and the galleries would set out a basket of magnifying glasses. You would see all these old ladies clustered around the paintings trying to see what was going on in the portholes."

His early illustration style has influenced many contemporary artists, including, Derek Yaniger, Shag (Josh Agle), Tim Biskup, children's book author Lane Smith ("I was always inspired by the spontaneity and animation in Flora's work"), and Pixar animator Pete Docter, along with such illustrators as J.D. King, Michael Bartalos, J. Otto Seibold, Phillip Anderson and Terry Allen.

Despite his reputation for humorous themes and penchant for caricature, and the undeniable influence of cartoon art on his work, Flora never created comics. He was, primarily, an artist, and incidentally, a humorist. J.D. King observed, "Even in Flora's fine art, there's a feel of the Sunday funnies, the Great American Comic Strip when it was actually great. And comical."

Born in Bellefontaine, Ohio, Flora attended the Art Academy of Cincinnati from 1935 to 1939. In 1938, he met writer Robert Lowry, then a student at the University of Cincinnati, and the two launched The Little Man Press, a letterpress series of limited edition publications, for which Flora supplied illustrations, design, and layout. They collaborated on Little Man Press until 1942. (Lowry, a volatile and self-destructive literary turbine, later self-published many works under a revived Little Man imprint without Flora's involvement.)

In 1941, he married his college sweetheart, artist Jane Sinnicksen. Following a brief, struggling period as a commercial artist in Cincinnati, Flora was hired at $55 a week by Columbia Records in 1942, at which time the Floras moved to Westport, Connecticut, since Columbia was then based in Bridgeport. (In 1945, the couple relocated to Rowayton, Connecticut, where they lived the remainder of their lives. They had five children.)

Beginning work in the art department under Alex Steinweiss, inventor of the illustrated album cover, Flora illustrated ads, new release bulletins, and retail and trade literature. In 1943, when Steinweiss entered the navy, Flora was promoted to Art Director. That year, he launched Columbia's monthly new release booklet, Coda, which he continued illustrating and designing through 1945, when he was promoted to advertising manager. His replacement as art director was Robert. M. Jones, who later became art director for RCA Victor (where he twice won the Grammy Award for Best Album Cover - Classical; Flora and Jones remained lifelong friends, their careers sporadically interwining). Flora's artwork began appearing on Columbia 78 rpm album covers in 1947 (not earlier, as some accounts allege).

Flora worked as advertising manager and sales promotion manager at Columbia, but felt ill-suited for bureaucracy and grew frustrated because he was working a desk job while doing little art. Finally reaching his endurance of what he called "endless meetings, endless memos, and wrestling with budgets," Flora resigned in 1950. "Bitten by the bug of wanderlust," he drove to Mexico with his family in a Hudson sedan. They remained south of the border for 15 months, during which time Jim and Jane painted, created woodcuts and lived as bohemian gringos in Taxco.