It was established in 1900 by a gift of historic keyboard instruments from Morris Steinert, and later enriched in 1960 and 1962 by the acquisition of the Belle Skinner and Emil Herrmann collections.

Initially housed under the dome of Woolsey Hall, it was moved in 1961 to a historic Romanesque structure on Hillhouse Avenue, constructed in 1895 for the Alpha Delta Phi fraternity.

In addition to presentations made to Yale classes, the Collection offers tours and lecture-demonstrations to school and private groups by appointment.

The annual concert series presented by the Collection of Musical Instruments features performers of music in its historical context, often using the appropriate instruments from the Collection that have been restored to playing condition.

Performers and ensembles that have appeared on the concert series include: The Alarius Ensemble, Malcolm Bilson, Anner Bylsma, The Flanders Quartet, John Holloway, Monica Huggett, Ralph Kirkpatrick, Jeanne Lamon, Gustav Leonhardt, Amsterdam Loeki Stardust Quartet, Paul O'Dette, London Baroque, Steven Lubin, Paolo Pandolfo, Phantasm, Stanley Ritchie, Jaap Schroeder, Fernando Valenti, and Marion Verbruggen.