Tcherepnin taught at the St. Petersburg Conservatory from 1905 to 1917, and among his students were Sergei Prokofiev, Alexander Gauk, Yuri Shaporin, Nicolas Obouchow and Lazare Saminsky.
In 1907, Nikolai wrote one his best-known works, the ballet Le Pavillon d'Armide. Two years later, he conducted it at the premiere performance of Sergei Diaghilev's Ballets Russes in Paris. He performed with the troupe for the entire first season in Europe and returned multiple times over the next five years, giving concerts in Berlin, Monte Carlo, Rome, and London. While conducting at the Mariinsky Theatre (1906–09), Nikolai Tcherepnin directed the Paris premiere of Rimsky-Korsakov's opera The Golden Cockerel.
He moved to Georgia in 1918 to become a director of the National Conservatory in Tbilisi. Following the Bolshevik takeover of Georgia in 1921, Tcherepnin immigrated to Paris and lived there for the rest of his life. In 1925, he founded the Russian Conservatory in Paris.