The first house for the Stroganovs was built on the site probably in 1720s. It was a building of one storey. Аrchitect Mikhail Zemtsov erected a second two-storey house in the 1740s.
In 1752 Baron Sergei Stroganov commissioned the palace design from Italian architect Bartolomeo Rastrelli, then at work extending the Catherine Palace and building the Smolny Convent for Empress Elisabeth. Since the Stroganovs were the richest family in Russia and were related to the Empress by marriage, Rastrelli could not turn down the commission and hastily prepared a design for the townhouse.
The main façade of the Stroganov palace faces Nevsky Prospect. Here, Rastrelli rejects the cour d'honneur in the French manner, like the one in the design of the Vorontsov Palace, built by Rastrelli in 1744-1750. By this time, Rastrelli has developed his own style based on exploring the impressive façade, which implies the presence of three risolites, the subordination to a single center, rejection of verticalization, and stretching the building horizontally. Rastrelli gives the building a single mass movement toward the center. He skillfully emphasizes this by subordinating the lateral risolites to the central, imposing group of columns of purely decorative, not architectonic, function, deliberately building up tension toward the center of the sculpted front.