While Martinů's esteem in Czechoslovakia was on the upswing, his reputation internationally fell into decline. This was triggered in part by his decision to uproot himself several times over the course of his final years. In 1952—with no reversal in the communist regime's stance against him—he took American citizenship, and the following year he left New York City for Europe, where he and Charlotte would eventually reside in Nice for two concert seasons. Despite the picturesque setting of the town on the French Riviera, Martinů was without intellectual contacts or friends, a situation that often left him lonely and in despair. He turned his attention to opera, first working on a number of trifles before discovering the value of adapting Nikos Kazantzakis's novel Christ Recrucified. This resulted in The Greek Passion, the work that occupied him throughout his final years. His return to the United States in 1955 for what would be his last concert season there was marked by discord with Frank Rybka, with whom he and Charlotte resided, and a brief and problematic teaching engagement at the Curtis Institute of Music in Philadelphia. His one-year fellowship at the American Academy in Rome, which he received so he could fully engage on The Greek Passion, formed the pretext for him to leave the United States permanently in 1956.

During his final stylistic period he developed a neo-impressionistic orchestral idiom. His breakthrough work, featuring an expanded orchestral palette and more rhapsodic forms, was Symphony no. 6 (“Fantaisies symphoniques,” 1953); other works for orchestra in a related style include Les Fresques de Piero della Francesca (1955); Fourth Piano Concerto (“Incantation,” 1956); Parables (1958); and Estampes (1958). Apart from the sonic transformation, these works also demonstrate a modified embrace of program music. In his Symphony no. 6, for example, he integrates material from his opera Julietta, Berlioz's Symphonie fantastique, and Dvořák's Requiem Mass, offering rich opportunities for extramusical interpretation. This he attempted to deny, however, which we see in his program notes to the work for the Boston Symphony Orchestra, where he focused exclusively on his principles of autonomous musical creation.