This story takes place in 1875 on until about 1878, it revolves around two famous ex Texas Rangers. The Rangers Captain Gus and Captain Woodrow Call run a boarding stable named the Hat Creek Cattle Company and Livery Emporium. This stable is located in a dust bowl town in Texas called Lonesome Dove. The two men are getting into their later years in life and decide to take one last journey together. This journey involves them driving cattle north out of Texas and to Montana. It is a journey in self discovery as along the way they loose people who were employees and friends, the aging men learn about themselves coming to important realizations. This cattle driving takes the guys through Oklahoma, Kansas, and Nebraska. It sees the cattle drivers meet new people, some good and some bad. It is in these meetings that they find out what their own strengths and weaknesses are, they fight for their lives battling storms, Native Americans, and US Calvary. In the end, however, Gus, who had been shot by arrows, succumbs to his injuries and dies. Call then returns to the town of Lonesome Dove to bury Gus.

Because the first book in the series, Dead Man's Walk,takes place in 1841, when Gus and Call were young Texas Rangers, it can be estimated that Lonesome Dove takes place 20-30 years later, probably in the late 1860s-early 1870s.