Krenek's music of the early 1920s (including the Symphony No. 1 from 1921 and the first two string quartets) is chromatically charged and rather angst-ridden; however, a 1924 trip to France, during which he was exposed to the more utilitarian, entertaining aspects of Parisian music (and Stravinsky's neo-Classicism in particular) encouraged him to explore a more accessible style. In 1927 the opera Jonny spielt auf, which fuses jazz idioms to Krenek's own brand of tonality, made Krenek a household name; the work was such a popular success that it eventually received performances in over a hundred cities in eighteen different languages.
From 1925 to 1927 Krenek lived in Kassel and Wiesbaden, serving as assistant manager of those city's operas. After returning to Vienna in 1928 Krenek began questioning his own musical aesthetic, and, upon meeting Alban Berg and Anton Webern, made a serious study of the Second Vienesse School's 12-tone techniques. By 1931, when he began composing the opera Karl V (in celebration of the unifying virtues of Catholicism, as opposed to the degeneration of Germanic society in the 1930s), Krenek was convinced of the merits of serial composition; the opera stands as his first thoroughly dodecaphonic work. Nazi officials were not oblivious to the political subtext of the opera, and the planned 1934 Vienna premiere of the work was canceled by the authorities. Krenek visited the United States in 1937, and when Hitler invaded Poland, Krenek was expelled from Austria and moved across the Atlantic permanently.
Krenek divided the remainder of his life between active composition (he remained prolific until his death in 1991) and teaching duties (first at Vassar College in New York, and later at Hamline University in Minneapolis and as guest professor/lecturer at many other American institutions). Krenek was an American citizen from 1945 on.
In the 1950s and 1960s Krenek began to explore electronic composition (e.g. Spiritus intelligentiae Sanctus for voices and electronic sounds in 1956), and also aleatoric (chance) music (e.g., the 1957 work Sestina). During the last decades of his life Krenek scrupulously avoided all compositional "trends" and "systems," choosing instead to rely on his own musical wits.
In 1992, one year after his death, Krenek's remains were transferred to the city of Vienna, where in later years he had come to be honored as befits a musician of his stature.