According to local tradition a congregation known as the O'Possum Creek Church built an all-faiths sanctuary in this area as early as 1858. During the 1860s the Macedonia community began to develop as English and German immigrants settled in the area. During the 1870s Macedonia developed into a thriving community consisting of the Macedonia Baptist Church, a Masonic lodge, a gin, a granary, and a general store.
A parcel of land which later included this cemetery was donated to the community by the S. A. Spiars family sometime prior to the first recorded burial here, that of J. C. Witt on April 22, 1874.
Macedonia residents and businesses began to disperse after the town of Granger was established about two miles east of here in the Missouri, Kansas and Texas Railroad in the early 1880s. Eventually, the last remaining physical evidence of the once-thriving community of Macedonia was this graveyard.
Macedonia Cemetery was abandoned until 1971, when descendants of people buried here formed a cemetery association to restore and preserve the graveyard. The cemetery remains in use and includes the burials of pioneers of this area and their descendants and veterans of the Civil War.