Nielsen began working on his Symphony No. 5 shortly after World War I. He was deeply affected by that terrible conflict, and the intensity of the Fifth may reflect the composer's feelings about war. At any rate, the work represents a significant shift in the composer's attitude and philosophy; many of his postwar pieces reveal an increasingly strident, polyphonic, and dramatic style, much in contrast to those of the pre-war era. Notably war-like is the dramatic content of the Fifth; conflicting moods and aesthetics are played out throughout: the consonant versus the dissonant, contrapuntal versus harmonic, constructive versus destructive. The work also represents a complete break from Classical form in favor of a two-movement structure; according to biographer Robert Simpson, the first movement contains "the crux of the conflict itself," while the second part is "a finale that would rise out of the ashes in a great fount of regenerative energy. Even this finale is not to be free of difficulties, but it is to prove irresistible in the end."

The first part of the symphony is divided into two contrasting sections: a Tempo giusto in common time and an Adagio non troppo in 3/4 time. A viola tremolo opens the work, a hypnotic perpetual motion figure that several brief melodies try to overrun. As other destructive forces encroach—a flurry of notes here, an obsessive snare drum rhythm there—the music reaches a chaotic peak and an Adagio section abruptly brings in constructive forces. Soon, however, the destructive element intrudes, and a veritable battle breaks out with the snare drum rhythm symbolizing the darker side of the conflict. The lyrical Adagio wins out, and the movement fades away with a peaceful clarinet melody, though still accompanied by the distant snare drum figure. An uneasy peace has been won as the second movement gets underway. The movement is divided into four main sections: the brisk opening Allegro subject surges along over an ostinato fourth motif in the bass, which leads into a scherzo-like Presto in the form of a fugue. Soon, destructive forces symbolized by the clarinet and tympani diminish the stability of this passage, and the more the music tries to continue in the face of these obstacles, the more frantic it becomes before an Andante passage finally introduces a second fugue. The subject is developed in a sonorous, polyphonic string texture before leading into a triumphant Allegro section that concludes the work on a note of exaltation and synthesis. "With the Fifth," Nielsen scholar Povl Hamburger asserted, "Nielsen reached the absolute summit of his creative power, not only in his symphonic, but in his instrumental music altogether. Nothing that was added afterwards equals it in greatness of mind, vision, and imagination."

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