In a small mid-Western town lives Cully, Matt Dillon, a mechanic by day and gambler by night. A wide-eyed innocent, he is far and away the best gambler in town. Under the advice of a friend, he packs his bags and heads to Chicago, The Big Town, to try his luck. Startled by the sheer size of the place, Cully befriends a couple who own a strip joint - Cole, Tommy Lee Jones, runs it while his wife Lorry, Diane Lane, is the headline attraction. Cully falls for her seductive powers but is also involved with a more stable young single mother, Annie. As he becomes aware that his world has a nasty side to it, he is forced to make a decision that will affect both his personal and professional life.

In Lonesome Dove, Texas former Texas Rangers Augustus 'Gus' McCrae and Woodrow F. Call are spending their time not doing much of anything. They have something of a reunion when old friends Jake Spoon and Joshua Deets arrive. They've not seen each other for something going on 10 years. Jake has an idea: they should round up a herd of cattle and drive them north where they could make their fortune. McCrae is a bit slow to come around the idea but they're soon crossing the border rustling horses and cattle that have been stolen by a Mexican bandit. By the time they're ready to set out, Jake Spoon has had a change of heart. He's been carrying on with Lonesome Dove's only saloon girl, Lorena Wood, and he's promised to take her to San Francisco. They're traveling more or less in the same direction so they're all going to be seeing each other quite a bit. The men on the cattle drive face long days and bad weather. One of them will not survive the first river crossing.