The first non-native burials occurred on the current University of Wisconsin–Madison campus. Later, other areas near campus were established as informal burying grounds and the first official village cemetery was established in 1847.  In the mid-1850's, the current site containing 80 acres of land was purchased.  In 1863 the city sold a portion of land to the Roman Catholic Societies, who in turn developed that property into a Catholic cemetery, now known as Resurrection Cemetery.  In the 1860's a receiving vault was built on site. During and following the Civil War, the Union Soldiers and Confederate Rest lots were created and in 1878 a chapel was built.  In 1928 another 80 acres were purchased, 60 of which are now part of a golf course located directly behind the present cemetery.  The cemetery also protects seven effigy mounds, dating from 700 to 1200 CE. The earthworks are shaped like a goose flying down a slope toward Lake Wingra, two panthers and a linear shape. Three more linear mounds were destroyed by cemetery development and the goose's head was destroyed by grading for the railroad. The mound group was listed on the National Register of Historic Places in 1974.

Within the Confederate Rest lot, located in the northernmost Confederate graveyard in the nation, lie around 140 Confederate Prisoners of War who died in 1862 while in confinement at Camp Randall, a Union camp, in Madison. In 1906 a stone marker, or cenotaph, was built and lists the names of 132 of these prisoners who died in custody. In October 2018, the Madison City Council majority voted to remove this marker from the cemetery, overturning the Madison Landmarks Commission, which had denied a permit to remove the marker. 

Additionally, there are several Jewish Bibles that have been buried here, all of which are located in Section 10 plots 44, 58, 62, 75, 76 and 77.