Settlers established the community of Saltillo around 1850 along the Old Jefferson Road, and John A. Arthur III and G.B. Hackleman opened the first stores while a post office began operation in 1860. Arthur is credited with naming the town after the capitol of the Mexican state of Coahuila. Land including the cemetery was conveyed from W.E. English to G.B. Hackleman in August 1871, and three months later G.B. and Wester Ann Hackleman deeded land to trustees to build a church for public worship by all denominations and for school purposes. The cemetery is first mentioned in a deed to trustees of the Methodist Episcopal Church, South, in 1894, after the town relocated to a new railroad site and the older settlement took the name Old Saltillo. The first known burial dates from 1870 but is unmarked, and many pioneer settlers and generations of their descendants are buried there. More than 100 veterans dating back to the Civil War have been identified, and the cemetery includes numerous granite markers as well as many marble markers for Woodmen of the World members. By the 1930s, families of those buried there gathered for an annual cemetery meeting, first on the third Thursday of July and changed in the 1960s to every third Sunday of July, and the Old Saltillo Cemetery Association officially formed in the late 1950s. Since Saltillo relocated in the late 1880s, the cemetery has served surrounding communities including Greenwood and Weaver, and in nearly 150 years more than 1,200 known graves have been documented, with likely many more early burials. Along with Old Saltillo United Methodist Church, it remains one of the few historic resources embodying the long history of this early Hopkins County settlement.