The opening scenes of Lonesome Dove take place at the Hat Creek Cattle Company, a small ranch in Lonesome Dove, Texas, just north of the Rio Grande. Hat Creek is operated by two old Texas Rangers, the taciturn Woodrow Call and the talkative Augustus “Gus” McCrae. Among their hands are the black scout Joshua Deets, the tall and lanky Pea Eye Parker, the teenage Newt Dobbs (who doesn’t know he is Call’s illegitimate child), and the reliable Dish Boggett and phobia-ridden Jasper Fant (who sign on a bit later).

The men spend a fair amount of time in the town’s saloon, playing cards and listening to the piano stylings of the forlorn Lippy Jones. Those with money to spend avail themselves of the favors of Lorena Wood, the prostitute whom a few of the men are in love with.

When Gus and Call’s old Texas Ranger buddy Jake Spoon shows up after a long absence, this sleepy scene begins to stir. Jake is on the run from July Johnson, an Arkansas sheriff who is the brother of a man he accidentally killed. Jake, a slick character, soon wins the love of Lorena, much to the consternation of her other suitors. He also mentions to Gus and Call that the Montana territory is ripe for exploitation, a seemingly trivial aside that winds up setting the plot in motion.

At Call’s insistence, the entire crew packs up and begins a cattle drive to Montana, where Call hopes to make his fortune. Lorena, desperate to leave Lonesome Dove, joins them, which leads to disaster when she is kidnapped by the Comanche outlaw Blue Duck and, after much hardship, rescued by Gus. (Lorena is hardly the only woman who is key to the narrative, which is one thing that distinguishes Lonesome Dove from many Western novels. As the crew passes through Nebraska, Gus visits his great lost love, Clara Allen, who turns out to be more than his match.)

The cattle drive is brutal and littered with corpses. The young Irishman Sean O’Brien is killed by snakes in the Nueces River, Jake is hanged by Gus and Call for horse thieving, and both Deets and Gus die after they are attacked by Indians. Gus’s final wish is for Call to carry his body back to Texas from Montana, which Call reluctantly does, bringing the story full circle.