Aaron Perry claimed the present site of Pioneer Cemetery and surrounding lands when Lawrence was founded in 1854. He allowed part of his land to be used as a burial ground called Oread Cemetery. Burials were without any system and may graves were unmarked and unrecorded, especially following Quantrill's Raid in August 1863, Many graves were moved to Oak Hill Cemetery, opened in 1865. Burials ceased at Oread Cemetery in 1882. In the 1880s, The Grand Army of the Republic furnished markers for the Wisconsin regiment (eighteen members died of typhoid fever in 1862) and an obelisk to unknown soldiers of the Civil War. For many years after that the area was not maintained.
In the 1950s the university purchased land west of Iowa Street for campus expansion. The area then known as Pioneer Cemetery was included at Chancellor Franklin Murphy's suggestion. The city deeded the property to the university with the stipulation that "the premises shall be forever maintained."
Former Chancellor and Mrs. Deane Malott donated much of the landscaping. The KU Endowment Association oversees the cemetery's maintenance and is responsible for its inurnment and campus use policies. Ashes of university personnel, graduates, and friends may be buried in urns under flat headstones following approval from KUEA.
In 2009 Historic Mount Oread Friends partnered with Frank Baron of the KU Max Kade Center for German-American Studies to repair the iron surround for and to landscape the Carl Rau 1855 gravesite. The surround is one of the oldest surviving examples of early ironwork in Kansas. It was broken in many places. Walt Hull, an expert in ironwork from Pleasant Grove, made the repairs.