St. Casimir's was established as a parish in 1902, becoming an independent parish in 1904. It was established to serve the needs of the growing Polish American community in Baltimore. The church building was built and dedicated in 1927. By that time the Poles were becoming so numerous in Baltimore that less than a year later another Polish Catholic church was established in a neighboring parish, the Holy Rosary Church. There were over 11,000 Polish immigrants living in Baltimore at the time.
In 2000, the St. Stanislaus Kostka church, another Polish Catholic church in Baltimore, was merged into St. Casimir's and the sacramental registers were transferred to St. Casimir's.