After Siloti's graduation it was decided that he would be sent to Weimar, Germany on scholarship to further his studies with Franz Liszt, co-founding the Liszt-Verein in Leipzig, and making his professional debut on 19 November 1883.

Returning to Russia in 1887, Siloti taught at the Moscow Conservatory, where his students included Alexander Goldenweiser, Konstantin Igumnov, Leonid Maximov, and his first cousin Sergei Rachmaninoff.

From 1901 to 1903, he led the Moscow Philharmonic; from 1903 to 1917, he organized, financed, and conducted the influential Siloti Concerts in St Petersburg, collaborating with the critic and musicologist Alexander Ossovsky.

In the generation prior to 1917, Siloti was one of Russia's most important artists, with music by Arensky, Lyadov, Blumenfeld, Szymanowski, Liszt, Rachmaninoff, Stravinsky, Taneyev and Tchaikovsky dedicated to him.

In 1918, Siloti was appointed Intendant of the Mariinsky Theatre, but late the following year fled what had become Soviet Russia for England, finally settling in New York City in December 1921.