Melrose is on State Highway 21 nine miles southeast of Nacogdoches in eastern Nacogdoches County. It was founded around 1840 by Dr. Thomas Jefferson Johnson, who is said to have named the town for Melrose Abbey in his native Scotland. The settlement, located on the Old San Antonio Road, became a stopping point on the road between Nacogdoches and San Augustine. A post office was established there in 1841, and by 1854 two schools were operating. By 1885 the community had a public school, a sawmill, two blacksmiths, three churches, three cotton gins, four general stores, five gristmills, and a population of 160. Melrose had 250 inhabitants by 1900. It began to decline after World War I; its post office closed in 1921, but in the mid-1930s the town still had seven businesses and 150 residents. After World War II the population level remained steady, though many of the businesses closed. In 1990 Melrose had two or three stores, several churches, a number of houses, and a population of 150. The population remained the same in 2000.