In 1860, Charles Rath took over the trading post of George Peacock on Walnut Creek, near present day Great Bend after Peacock and five others were massacred by Kiowa warriors led by Satank. Rath also began to operate a sutler’s store at nearby Fort Zarah and in November, 1860 was elected constable of Peketon County (later part of Marion County.) From the time that Rath came west he had begun to establish trading contacts with a number of Indian tribes, including the Southern Cheyenne, Kiowa, and northern Comanche bands. He strengthened those alliances when he married a Cheyenne woman in 1860. The couple would have one daughter in 1861.  

In 1863, he partnered with several men to build a toll bridge across Walnut Creek. About this same time, tensions between the Indians and the white settlers mounted and even though Rath had done his best to maintain peaceful relationships with the tribes, his Walnut Creek Trading Post was raided several times. For his own safety, his Cheyenne wife convinced him to divorce her.

In the late 1860s he and his hired teamsters hauled freight for the military posts along the Santa Fe Trail and for the troops and government agencies in western Indian Territory. He and others also hunted game and buffalo for the railroad workers in Kansas. He also began to invest in Kansas real estate.

In 1869 he made a return visit to his old home in Ohio, where he met Caroline Markley, whom he married on April 26, 1870. The couple would eventually have three children. Returning with her to Kansas, the couple lived briefly in Topeka, then at Osage City, where Rath established a mercantile business and continued his freighting.

In the early 1870s Rath was one of the first men to take advantage of the growing buffalo hide trade and in September, 1872, he moved his family to Dodge City. He soon began hunting, freighting, and marketing the hides and formed the Rath Mercantile Company, whose yard was sometimes filled with as many as 80,000 hides at one time. When Ford County was officially organized in 1873, Rath became one of its first three commissioners.

As the buffalo diminished in Kansas, he began to hunt in the Texas Panhandle and with Robert M. Wright and James Langton, made plans to build a store and restaurant at Adobe Walls, near the site of William Bent's old outpost. Soon a three-room sod building was almost completed and the store was furnished with goods. Just as it was almost complete, Rath and his men returned to Dodge City in May, leaving three men and a woman to mind the store. He was safely back in Dodge City when a combined force of some 700 Comanche, Cheyenne, Kiowa, and Arapaho warriors attacked the post on June 27, 1874, in what is known as the Second Battle of Adobe Walls.