He made his first appearance as a conductor at age 15.
He became musical director of the RIAS Symphony Orchestra RIAS Symphonie-Orchester Berlin in Germany in 1949, and of the Houston Symphony Orchestra in 1954. From 1956 to 1958 he was music director of the Bavarian State Opera Bayerisches Staatsorchester (1956–1958).
From the 1950s until his death, he recorded for the Deutsche Grammophon record label.
Fricsay was known for his interpretations of the music of Mozart and Beethoven, as well as that of his teacher Béla Bartók. His 1958 recording of Beethoven's Symphony No. 9 is featured in the movie A Clockwork Orange.