Cowles founded Flair magazine in 1950, and it folded a year later. The magazine, which Time described at its launch as "a fancy bouillabaisse of Vogue, Town & Country, Holiday, etc.," was celebrated not only because of its design and editorial production by European art director Federico Pallavicini (né Federico von Berzeviczy-Pallavicini) but also because of its lavish production. It was the resulting cost of production that killed the magazine, since the expensive special costs (for cover cut-outs for some issues, for example) could not be supported in the long run.
Contributors included W. H. Auden, Simone de Beauvoir, Winston Churchill, Jean Cocteau, Salvador Dalí (The Gypsy Angels Of Spain), Lucian Freud, Clare Boothe Luce, Ogden Nash, Saul Steinberg, Rufino Tamayo, Tennessee Williams, and Angus Wilson.
In later decades, Cowles served on various government committees and represented Dwight D. Eisenhower at the coronation of Elizabeth II. She was a member of the Founding Council of the Rothermere American Institute at Oxford University. In 1996, the book The Best of Flair collected much of the material from the magazine she founded. Her paintings from the books Tiger Flower and Lion and Blue are to be made into three-dimensional computer-animated films.