Simbirsk was founded in 1648 by the boyar Bogdan Khitrovo.The fort of "Simbirsk" (alternatively "Sinbirsk") was strategically placed on a hill on the Western bank of the Volga River. The fort was meant to protect the eastern frontier of the Russian Empire from the nomadic tribes and to establish a permanent Imperial presence in the area.
In 1668, Simbirsk withstood a month-long siege by a 20,000-strong army led by rebel Cossack commander Stenka Razin. Also in Simbirsk another country rebel, Yemelyan Pugachev, was imprisoned before execution. At the time Simbirsk possessed a wooden kremlin, which was destroyed by a fire during the 18th century.
As the eastern border of the Russian Empire was rapidly pushed into Siberia, Simbirsk rapidly lost its strategic importance, but nonetheless began to develop into an important regional center. Simbirsk was granted city status in 1796.
In the summer of 1864, Simbirsk was severely damaged by fire; however, it was quickly rebuilt and continued to grow. The Holy Trinity Cathedral was constructed in a restrained Neoclassical style between 1827–1841. The population of Simbirsk reached 26,000 by 1856 and 43,000 by 1897.
In 1924, the city was renamed Ulyanovsk in honor of Vladimir Ulyanov, better known as Lenin, who was born in Simbirsk in 1870. Two other Russian political leaders, Alexander Kerensky and Alexander Protopopov, were also born in Simbirsk.