The MCHC has been located at the Enoch Pratt House in the Mount Vernon neighborhood of Baltimore, Maryland, since 1919.

Notables on exhibit at the MCHC are the original manuscript of "The Star-Spangled Banner" and the letters and journals of Benjamin Banneker.

The MCHC showcases include 231 weapons, 866 pieces of jewelry, 2,200 Native American prehistoric archaeological objects, 15,000 musical scores as well as a remarkable collection of 18th- and 19th-century paintings and silver, maritime artifacts, Maryland painted and inlaid furniture, quilts, costumes, ceramics, dolls and toys.

In 1968 the library acquired 80 photographs by Bert Sadler, noted for his work in capturing everyday American life.

[citation needed] The MCHC is a community partner of Preserve the Baltimore Uprising, a digital archive devoted to preserving and making accessible media created and captured by people and organizations involved in or witness to the protests following Freddie Gray's death in 2015.