The building is named for Dr. Henry Plummer, widely-regarded as the Architect of the Mayo Group Practice. He joined the Mayo in 1901 and designed many of the systems that gave rise to the group practice concept that has become so successful.

The main library reading room on the 12th floor is called Mayo Hall. Dr. Plummer selected sixty prominent physicians and scientists to be memorialized with their names engraved in the room's ceiling beams.

The Plummer Building was the tallest building in Rochester from 1929 until completion of the Gonda Building in 2001.

It was added to the National Register of Historic Places in 1969.

The first two stories are of limestone, while the upper ones are of brick with terra cotta trim.

The tower holds a 56-bell carillon, enlarged in 1977 from the original 23-bell carillon dedicated on 16 September 1928.

Luis Walter Alvarez, solo winner of the Nobel Prize for Physics in 1968, illegally climbed to the top of the building's steel framework while under construction. He was still a teenager.