Although he specialized in the Byzantine-Bulgarian relations and investigated the Slavic influence on the Byzantine economy, Uspensky also researched and wrote extensively on the Crusades.

In 1894 Uspensky, who shared Slavophile ideals, decided to move to Constantinople to study and protect the surviving monuments of Byzantine antiquity, which had been neglected by the Ottoman authorities for centuries.

Back in Petrograd, the 70-year-old professor was invited to edit the organ of Byzantine studies, Vizantiyskiy Vremennik.

After the October Revolution, he delivered lectures at the Leningrad University (1922–27) and prepared for publication the results of a lifelong study, a monumental three-volume account of the history of the Byzantine Empire.

The posthumous publication of his magnum opus, based on numerous unpublished sources and unprecedented in scope, demonstrated the wide range of his scholarship.