Gus is a former Texas Ranger and co-owner of the Hat Creek Cattle Company in the small border town of Lonesome Dove. He possesses a whimsical, argumentative nature and actively avoids hard labor. Despite his apparent laziness, he is a fiercely loyal friend and a highly capable fighter when danger arises. He prefers reading the Bible to annoy others and spending time at the local saloon over running a ranch.

Call is a taciturn, hard-working former Texas Ranger who co-owns the Hat Creek Cattle Company. He operates strictly out of a rigid sense of duty and struggles to express emotion or feel comfortable in social situations. Restless in the quiet town of Lonesome Dove, he seizes on the idea of driving a massive herd of cattle to Montana to find a new purpose and experience untamed country.

Newt is an orphaned teenager working at the Hat Creek Cattle Company. He idolizes Call and Gus, desperately seeking their approval and wishing to be treated as a full-fledged cowboy rather than a boy. He longs for adventure and family connection, dealing with ongoing uncertainty about who his father actually is.

Jake is a handsome, smooth-talking former Texas Ranger who loves fine clothes, gambling, and beautiful women. He arrives in Lonesome Dove on the run from the law after accidentally shooting an unarmed dentist in Arkansas. He uses his charm to manipulate others, prioritizing his own comfort and safety over loyalty or responsibility.

Clara is a fiercely independent and intelligent rancher living near Ogallala. She has survived massive personal tragedies, including the loss of multiple sons and a severe injury to her husband that left him an invalid. She runs her property with total competence and holds little patience for men who act foolishly or lack clear direction.

Lorena is a quiet, strikingly beautiful young woman who works as a sporting girl in Lonesome Dove. A history of severe abuse has left her guarded and distrustful of men. She views the arrival of Jake Spoon and the upcoming cattle drive as her perfect opportunity to escape her current life and start over in California.

Blue Duck is a ruthless, highly intelligent bandit operating in the open territories. He harbors a decades-long grudge against Gus and Call from their days as Rangers. He leads a dangerous group of outlaws and utilizes fear, extreme violence, and intimidation to control the plains.

July is the young, mild-mannered sheriff of Fort Smith, Arkansas. He is thrust into a difficult situation when Jake Spoon kills his brother-in-law. Although he is devoted to his family and his job, he lacks the worldly experience necessary to handle the brutal realities of the open frontier once he begins his pursuit.

Pea Eye is a tall, awkward ranch hand who served with Gus and Call in the Rangers. He is slow in thought and easily confused by Gus's humor, but he is completely reliable and content to follow orders. He feels deeply uncomfortable around women and routinely fears encounters with hostile forces on the trail.

Deets is a Black man who has worked with Gus and Call for years as their primary scout and tracker. He is highly capable, patient, and sensitive to omens. Despite his immense value to the outfit and his unmatched knowledge of the land, racial prejudice ensures he rarely receives formal authority.

Elmira is July's wife, a former sporting girl who married him out of convenience rather than love. She is selfish, robotic in her responses, and completely dissatisfied with her safe life in Arkansas. She harbors an intense obsession with her former partner and actively plots to abandon her current family the moment July leaves town.

Dish is a highly skilled, 22-year-old cowboy who joins the Hat Creek cattle drive. He is hopelessly infatuated with Lorena Wood, willing to spend his entire month's wages just to sit near her. He hopes the journey north will give him a chance to prove his immense worth and win her affections.

Roscoe is the 48-year-old, bumbling deputy of Fort Smith. He is deeply uncomfortable with travel, responsibility, and conflict. When forced by the townspeople to leave Arkansas to find July, he stumbles through the wilderness, relying entirely on luck and the help of eccentric strangers to survive.

Joe is Elmira's 12-year-old son. He is thrilled to accompany his stepfather on a dangerous manhunt, viewing the trip as an exciting adventure far away from his mother's coldness and the boredom of town life.

Janey is a tough, resourceful young girl who escapes from an abusive captivity to travel with Roscoe. She is capable of catching game, traveling long distances barefoot, and fending off attackers with rocks, proving far more suited to the wilderness than the deputy she accompanies.

Sean is a young Irish immigrant who accidentally crosses paths with the Hat Creek crew during a nighttime raid in Mexico. Homesick, deeply emotional, and unaccustomed to the harsh environment of the West, he joins the cattle drive out of necessity and a lack of better options.

Allen is an Irish immigrant who travels the unforgiving frontier with his brother. He relies on the Hat Creek outfit for employment and physical protection after they lose their few possessions on the border.

Wilbarger is an educated, tough horse trader and rancher. He enjoys reading classic literature and verbally sparring with Gus. He offers pragmatic advice about the massive dangers of the trail and serves as a highly capable presence on the plains.

Xavier is the emotional, easily upset owner of the Dry Bean Saloon. He is deeply and hopelessly in love with Lorena, weeping openly and pleading with her when she decides to leave his establishment.

Lippy is a piano player with a prominent bottom lip who works at the local saloon in Lonesome Dove. He provides background noise for the quiet town and eventually decides to follow the cattle drive simply to avoid staying behind alone.

Po Campo is an eccentric cook who refuses to ride animals and prefers to walk alongside the wagons. He prepares unusual meals, including fried grasshoppers, and possesses a mysterious past with a reputation as a fortune teller.

Big Zwey is a massive, slow-witted buffalo hunter. He fixates on Elmira during a boat ride and simply decides he is going to marry her, following her relentlessly across the country and providing brutal physical protection when necessary.

Dan is a vicious outlaw and murderer who runs a small gang. He steals horses, kills without hesitation, and forces those around him to participate in his violent crimes through intimidation.

Maggie was a sporting girl in Lonesome Dove who died of a fever prior to the events of the novel. She was deeply in love with Call and gave birth to Newt, hoping Call would finally acknowledge him and form a family.

Peach is July's highly belligerent sister-in-law. After her husband, the mayor, is killed, she aggressively badgers July and Roscoe to enforce the law, showing no sympathy for their limitations or hesitations.

Bob is Clara's husband, a former horse trader who suffered a severe brain injury after being kicked in the head by a horse. He is now an invalid, entirely dependent on his wife for care.

Dee Boot is Elmira's former partner and Joe's biological father. He is a gambler who provided Elmira with money to change her identity years ago, becoming the sole focus of her desires.