McCrae, a respected physician and noted professor of medicine at McGill University, is best remembered as the author of In Flanders Fields. This famous poem of World War I, was written while he was a member of the Canadian Army Medical Corps.

McCrae House was a project of the Col. John McCrae Birthplace Society, an organization dedicated to creating a museum of the birthplace of John McCrae. The Society's dream was realized in 1968 with the official opening of the museum. In 1983 this museum was amalgamated with the Guelph Civic Museum to form Guelph Museums.

Over the years, objects, photographs and documents were collected that relate to the life of John McCrae and his ancestors. The museum consequently has a collection of mid to late 19th century and early 20th century materials: letters, diaries, journals, sketch books, documents, photographs, uniforms, furniture, medical equipment, etc. Two rooms (a kitchen and a bedroom) portray middle class life in 1870s Guelph. The rest of the museum consists of an "L" shaped gallery that depicts the life of John McCrae and his family. A late 19th century board and batten coach house is located behind the main building.

The national significance of the site is recognized by the National Historic Sites and Monuments Board of Canada. The house has also been designated by the City of Guelph as a building of architectural and historic value under the Ontario Heritage Act.