Born in Prague of Jewish-German origin, Schulhoff was one of the brightest figures in a generation of European musicians whose successful careers were prematurely terminated by the rise of the Nazi regime in Germany. The contributions made by many of these musicians, including Schulhoff, have largely languished in obscurity ever since, despite their pivotal importance to the development of classical music during the early 20th century.

In his youth, Schulhoff studied composition and piano in Prague, Vienna, Leipzig and Cologne. He began to embrace the avant-garde influences of jazz and Dadaism in his performance and writing after World War I. He was one of the first classical composers in Europe to find inspiration in the rhythms of jazz music. Schulhoff was a celebrated keyboard virtuoso and made extensive tours of Germany while also venturing farther afield to France and England.

In the 1930s, Schulhoff ran into mounting personal and professional difficulties. Because of his Jewish descent and his radical politics, he and his work were blacklisted as "degenerate" by the Nazi regime. He could no longer give recitals in Germany, nor could his works be publicly performed.

His Communist sympathies, which became increasingly visible in his works, also brought him trouble in Czechoslovakia. In 1932 he created a music version of "The Communist Manifesto" (Op. 82). Taking refuge in Prague, he found employment as a radio pianist but earned barely enough to cover the cost of everyday essentials. When the Nazis invaded Czechoslovakia in 1939, he had to resort to performing under a pseudonym. In 1941, the Soviet Union approved his petition for citizenship, but he was arrested and imprisoned before he could leave Czechoslovakia.

In June 1941, Schulhoff was deported to the Wülzburg concentration camp, near Weißenburg, Bavaria. He died on August 18, 1942 from tuberculosis.