Osage is on the north and middle forks of Harvey Creek, four miles northeast of Weimar in northwest Colorado County. Much of the land was originally included in grants to Henry Austin, a cousin of Stephen F. Austin. Settlement along Harvey Creek began in 1851 with the arrival of the Tom Hubbard family from Mississippi. In 1855 they were joined by a thirty-six-wagon caravan that brought many other families of Scottish, English, and Irish extraction from the Laurel, Mississippi, area. In 1856, after the first homes were built and the first crops harvested, Dr. Samuel D. McLeary named the new community Osage, for the luxuriant growth of bois d'arc, or osage orange, trees in the area.
During the Civil War Osage and other communities along Harvey Creek furnished most of the men and horses for Company A, Fifth Texas Cavalry, Confederate States of America. A Confederate post office was established in 1862, and the community had several stores, a blacksmith shop, a gin, and many substantial homes. Osage was the site of a school established by E. B. Carruth in 1874. A student later praised the school's curriculum as "the best selected of any I have ever known. It included Webster's Blue Back Spelling Book, all of the McGuffey Readers, history, geography, grammer, rhetoric, elementary and higher mathematics and Latin." Students came from a 100-mile radius and boarded with families in the area.
In 1873 when the Galveston, Harrisburg and San Antonio Railway built west from Columbus, Weimar was founded about four miles southwest of Osage, and business moved to the railroad. By 1900 all business was gone. As of the mid-1980s Osage consisted of many small farms and grazing operations and the homes of a few people who worked in town but preferred rural living.