He became co-owner with his brother John of the Cowles Media Company (established in 1935), and in 1937 became co-founder, co-publisher, and editor of Look magazine. He also served as executive editor of The Des Moines Register and The Des Moines Tribune.
In 1939, Mike and John, along with entrepreneur Everett M. "Busy" Arnold, became owners of the newly formed Comic Magazines, Inc., the corporate entity that would publish the Quality Comics comic book line. (Quality was an influential creative force in what historians and fans call the Golden Age of comic books).
In 1942 Cowles had been appointed to wartime duty as assistant director of the Office of War Information.[5] His responsibilities in the OWI were to direct a domestic news bureau, coordinating information from non-military government agencies. Cowles served in the OWI under the leadership of Elmer Davis for about a year and then returned to Des Moines.[2]
In the fall of 1942 Cowles and Barnes accompanied Willkie, who was serving as special representative of President Roosevelt, in his international tour (North Africa - Beirut - Jerusalem - Soviet Union - Siberia - China). They visited Stalin in Moscow on September 23, 1942[6]
Returned to USA Cowles had 2-hours press conference in November 1942 and told how Stalin allegedly expressed anti-British sentiment.[7] Stalin denied the accusation.[8]
In his 1985 memoir Mike Looks Back Cowles claimed Willkie had asked him to cover for him during an assignation with Madame Chiang. The two had absented themselves from a banquet, Cowles said, leaving him to confront an angry generalissimo and three of his gun-wielding bodyguards—later inflated to 'sixty' in Washington gossip circles—who searched the guesthouse and found nothing.[9]
Cowles was a donor to the Gardner Cowles Foundation, an executive of the Farfield Foundation (supposedly a CIA front),[12] and sponsor of the journal History.
Cowles was married to writer, editor, and artist Fleur Cowles from 1946 to 1955, ending in divorce.[4] His daughter Lois Cowles Harrison (1934–2013) was a civic leader, women's rights activist, and philanthropist. He was married to Jan Hochstraser (also known as Jan Streate Cox) from May 1956 until his death and had a daughter Virginia and stepson Charles, an art dealer.[14]