Chillicothe is a city in Hardeman County, Texas, United States. The population was 549 at the 2020 census. Chillicothe is on U.S. Route …Chillicothe is a city in Hardeman County, Texas, United States. The population was 549 at the 2020 census. Chillicothe is on U.S. Route 287, Farm to Market Road 91, Farm to Market Road 2006, and the Fort Worth and Denver and Santa Fe railroads in eastern Hardeman County. It was founded in the early 1880s and developed rapidly after the construction of the Fort Worth and Denver City Railway in 1887. The community, named by A. E. Jones for his hometown in Missouri, grew up on Wanderer's Creek near the headquarters of W. H. Worsham's R2 Ranch in the 1870s. The post office was established in 1883 with Charles E. Jones as postmaster. A fire destroyed the town in 1890, and citizens rebuilt south of the rail line rather than north.