At the age of six Björling began singing under the guidance of his father, who then took him and his two brothers on tours in Scandinavia and the United States as a vocal quartet. At 17 he began his studies at the Royal Opera School in Stockholm, where he made his operatic debut in 1930 as Don Ottavio in Mozart's Don Giovanni. He appeared as guest performer in several opera houses in Europe before achieving a huge success at Covent Garden, London, in 1936. In the following year he gave his premiere performances in the United States, first on the radio, then on stage in Chicago.

In 1938 Björling made his Metropolitan Opera debut as Rodolfo in Puccini's La Bohème, a role he repeated in 1940 in San Francisco. He sang with the Metropolitan Opera from 1938 to 1941, and, after spending the war years in Sweden, he returned in 1946 to sing with the Metropolitan company until his death. He continued to perform in Sweden between seasons at the Metropolitan. His popular concerts and prolific recordings won him fame as a recitalist and soloist in symphonic choral works. His autobiography, Med bagaget i strupen (“With My Baggage in My Throat”), was published in 1945.