As Olga Samaroff, she self-produced her New York debut at Carnegie Hall in 1905 (the first woman ever to do so). She hired the hall, the orchestra, and conductor Walter Damrosch, and made an overwhelming impression with her performance of Tchaikovsky's Piano Concerto No. 1. She played extensively in the United States and Europe thereafter.  It was Samaroff who discovered Leopold Stokowski (1882–1977) when he was church organist at St. Bartholemew's in New York and later conductor of the Cincinnati Symphony Orchestra. She played Tchaikovsky's Piano Concerto No. 1 under Stokowski's direction when he made his official conducting debut in Paris with the Colonne Orchestra on May 12, 1909.

She married Stokowski in 1911, and their daughter Sonya was born in 1921. At that time, Samaroff was much more famous than her husband and was able to lobby her contacts to get Stokowski appointed in 1912 to the vacant conductor's post at the Philadelphia Orchestra, thus launching his international career. Samaroff made a number of recordings in the early 1920s for the Victor Talking Machine Company. She was the second pianist in history, after Hans von Bülow, to perform all 32 Beethoven piano sonatas in public, preceding Artur Schnabel (who did the series first in 1927) by several years.