The building was designated a National Historic Landmark in 1976, in honor of the murals on its walls that were painted by Robert S. Duncanson under the commission of Nicholas Longworth.

Robert S. Duncanson painted the series of eight large-scale landscapes directly on the plaster walls of the art patron and horticulturist Nicholas Longworth's home between 1851 and 1852.

In the Tafts' deed of gift they stated, "We desire to devote our collection of pictures, porcelains, and other works of art to the people of Cincinnati in such a manner that they may be readily available for all."

[10] The museum's collections include European old master paintings, with works by Jean-Baptiste-Camille Corot, Thomas Gainsborough, Frans Hals, Jean Auguste Dominique Ingres, Rembrandt van Rijn, Adriaen van Ostade, and J. M. W. Turner, among others, and 19th-century American paintings, including the well-known Duncanson murals.

The galleries in the historic house also include Chinese porcelains, European decorative arts, Limoges enamels, watches, sculptures, and furniture.