Born in Valencia, Spain, Iturbi showed a talent for classical music at an early age, and began musical studies there. He later moved to Paris in order to proceed with his studies with Victor Staub at the Paris Conservatory on a scholarship from the Diputació de Valencia. At this time, he also undertook studies in keyboard technique and interpretation with the harpsichordist Wanda Landowska. His worldwide concert tours, beginning around 1912, were very successful. He made his American debut in New York City in 1929.
Between 1911 and 1937, he was the frequent accompanist to the Spanish violinist Manuel Quiroga on his international tours. On 8 June 1937, he had just said goodbye to Quiroga after a concert in New York when the violinist was hit by a truck in Times Square, which led to the premature end of his career.
Iturbi made his first appearance as a conductor in Mexico City in 1933 when presented by impresario Ernesto de Quesada from Conciertos Daniel. In April 1936, Iturbi was injured in the crash and sinking of Pan American Airways' Puerto Rican Clipper in Port-of-Spain, Trinidad. After the incident, he said he would not be able to play "for some time", and "I may not be able to conduct again." Later that year, he was named conductor of the Rochester Philharmonic Orchestra in Rochester, New York, serving until 1944. He also led the Valencia Symphony Orchestra for many years.

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