Founded by the Jesuits and dedicated to St. Casimir, construction of the church began in 1604. Povilas Bokša, the assistant provincial and Jan Prockowicz, a Jesuit architect oversaw the work. The church was finished and consecrated in 1635. It burned down in 1655, when the Russian army entered Vilnius. The church was twice more destroyed by fire in 1707 and 1749.

The famous architect and astronomer Tomas Žebrauskas, SJ, headed the reconstruction of the church in 1749-55. His work can be seen in the graded cupola and the main altar. From 1751 to 1753 Hans Kierner, a Prussian sculptor, decorated the interior. Frescos of St. Casimir's life were painted by the Czech artist Joseph Obst.

When the Society of Jesus was suppressed in 1773 (it was reinstated in 1814), the church was given to the Augustinians. In 1812 the French army turned the church into a grain silo, destroying the altars, statues and paintings. In 1815 the church was given to missionary priests, who cleaned up the interior and added eleven altars.

The missionaries were banished in 1832, and the church remained vacant and unused. In 1839 the Russians turned it into an Orthodox church known as St. Michael's. It was reconstructed in 1864-68 under the architect N. Chiagin, who lowered the steeples, added a larger steeple in the front, and covered all the steeples and the cupola with onion domes. The main facade was decorated in Neo-Baroque; frescos of Orthodox saints were painted in the three niches.

In 1915 the German army turned the church into a Lutheran house of worship for their army. In 1917 the church was returned to the Catholics. The German Jesuit Friedrich Muckermann energetically organized spiritual and social agencies for the people, for which work he was deported to prison in Minsk by the Bolsheviks.

In 1919 Blessed George Matulaitis returned the church to the Jesuits. Its restoration in 1925 was overseen by the architect Jan Borovski.

From 1940 the Lithuanian Jesuits worked in the church. In 1942 the crown on the cupola, a symbol of Lithuanian independence, was restored under the architect Jonas Mulokas.

In 1949 the church was again closed, this time by the Soviets, who stored grain in it. At this time the entire inventory of the church was destroyed, including the altars, organ, and bells. In 1963 the church was turned into a museum of atheism.

The church was returned to the Roman Catholic community in 1988. After intense restoration the church was reconsecrated in 1991, and the Jesuits again work in it.