The history of the museum began in 1963 when a literary museum was established on a voluntary basis by the Kirov Writers' Organization. Writers, book lovers, local historians, and long-time residents of Kirov participated in its formation.

The first exhibition opened in the spring of 1967 at the A. I. Herzen Library. A year later, the museum was provided with premises in the house where M. E. Saltykov-Shchedrin lived in exile from 1848 to 1855. Today, it is a monument of federal historical and cultural significance.

On October 25, 1968, the Kirov Literary Museum was officially opened, based on the writer's memorial study. In 1971, the museum became a department of the Kirov Regional Local History Museum. In 1980, after the opening of the A. S. Grin Museum, the literary museum was transformed into the M. E. Saltykov-Shchedrin House Museum. In 1997, a new exhibition was created, including authentic 19th-century items from the provincial government and homes of the writer's acquaintances in Vyatka, rare editions of books, magazines, newspapers, as well as photographs and documents from that time.

The memory of the writer is preserved in the publications of his works, in the works of contemporary artists and photographers who captured the places where M. E. Saltykov-Shchedrin lived and worked.

The museum preserves literary traditions: it celebrates the anniversaries of local writers, hosts meetings with Kirov writers and poets, literary evenings, and opens exhibitions dedicated to important events in the city's literary life. Among the museum's exhibitions is "The People's Writers of Latvia in the Kirov Region," which tells about Jan Rainis's exile to the Vyatka province and the lives of Latvian writers in the Kirov region during the Great Patriotic War, as well as "The History of the Book and Writing in Vyatka Land." Today, the museum's activities are aimed at attracting visitors of different ages and interests.

The M. E. Saltykov-Shchedrin House Museum, together with the A. I. Herzen Regional Scientific Library, organizes Saltykov Readings in Kirov.

The museum has become one of the cultural centers of the city, beloved and respected by the residents and guests of Kirov.