- Captain Woodrow F. Call – A co-owner of the Hat Creek outfit and former Texas Ranger, he is a largely silent leader of men and tireless worker who believes firmly in discipline, duty, and honor; he is a foil to his best friend Gus. In his preface, McMurtry describes Call as a Stoic.[4]
- Captain Augustus "Gus" McCrae – A co-owner of the Hat Creek outfit and former Texas Ranger, he is a lazy, loquacious, and charismatic rake with a fondness for alcohol, gambling, and whores; he is nonetheless a brave and competent fighter when required. He is tall and lanky, famed for his excellent eyesight, and has had silver hair since he was 30. He serves as a foil to his best friend, Call, and is described by McMurtry as an Epicurean.[5]
- Pea Eye Parker – The wrangler and blacksmith of the Hat Creek Cattle Company, Pea Eye served as a corporal in the Rangers under Gus and Call. Pea Eye (his real first name long forgotten) is not especially bright, but he is brave, reliable, and kind. He follows Call's lead without question.
- Joshua Deets – An African-American former Ranger, Deets is a loyal ranch hand, and on the drive serves as the chief scout. He is an exceptional tracker who relies on his phenomenal instincts to lead the company out of harm's way. He is quiet and contemplative, but wise, compassionate, and trusted by all.
- Newt Dobbs – A 17-year-old orphan, he was raised by Gus and Call. His mother was a prostitute named Maggie, who died when he was a child. He knows his mother was a prostitute, but has no idea who his father might be. Most observers, notably Gus and Clara Allen, are confident Call is his father. Though he begins the journey awkward and inexperienced, Newt develops into a competent and reliable cowboy, and despite his young age, is eventually given leadership of the ranch in Call's absence. In his preface, McMurtry refers to Newt as "the lonesome dove of the title."[6]
- Jake Spoon – A former Ranger, he left his friends 10 years ago to travel around America, returning to Texas near the beginning of the novel. Like Gus, Jake is a drinker, gambler, and womanizer. He possesses a great personal charm, but is lazy, selfish, and often careless.
- Dishwater "Dish" Boggett – Though only 22, Dish is a cowboy of great skill and the "top hand" for Call's cattle drive. He suffers greatly from unrequited love for Lorena Wood. His nickname derives from once having drunk dishwater on a cattle drive, being so thirsty that he could not wait for the water barrel.
- Bolivar – A former Mexican bandit and the cook for the Hat Creek Cattle Company, he is obsessed with loudly and unnecessarily ringing the dinner bell to call the company for dinner. Bolivar is uneasy about venturing far from the Rio Grande and abandons the cattle drive before it leaves Texas.
- Po Campo – The cattle drive's enigmatic new cook, he was hired by Call in San Antonio after Bolivar's departure. He uses exotic ingredients such as grasshoppers in his meals and refuses to ride animals. He hints at being well-traveled, and also offhandedly remarks that he killed his wife.
- Lorena Wood – A beautiful young woman from Alabama, she was coerced into prostitution by a former lover, later washing up in Lonesome Dove, where she works as the town's only whore. Lorena is taciturn, strong-willed, and often intimidating to the numerous cowboys who seek her affection, generally viewing her clients and admirers with contempt. Discontented with her life, Lorena initially harbors a dream of traveling to San Francisco, but her perspective changes dramatically after her experiences during the cattle drive.
- Blue Duck – The son of Comanche war chief Buffalo Hump and his Mexican captive, Blue Duck leads a gang of renegade Indians and Caucasian criminals. Atrociously wicked and remorseless, he is feared across the plains as a ruthless murderer, rapist, and slaver. He has managed to evade the law even as the West gradually grows safer and more civilized.
- July Johnson – The sheriff of the town of Fort Smith, Arkansas, July is a kind young man recently married to Elmira, whom he deeply loves despite her being openly disdainful of him. After his brother Ben is accidentally killed by Jake Spoon, July sets off in pursuit of him.
- Elmira Johnson – A former whore from Kansas, she recently married July Johnson. She is unhappy with her life and suffers from depression, eventually leaving Fort Smith to seek out her old love Dee Boot.
- Roscoe Brown – The deputy sheriff of Fort Smith, Arkansas, Roscoe is a simple man in his 40s who is content to spend his life minding the sleepy town's jail, but is bullied by July's sister-in-law into tracking down the sheriff and his missing wife.
- Joe – Elmira's son, he travels with July to find and arrest Jake Spoon.
- Janey – A young girl whom Roscoe meets on his journey to find July, she was a slave to an old man living alone in the woods, but when Roscoe arrives, she escapes from captivity and travels with him, proving herself useful with her ability to catch animals to eat and her excellent aim when throwing rocks.
- Clara Allen – Gus' former love, she declined his repeated marriage proposals during their youth in Texas – for reasons that were never entirely clear to Gus – instead marrying the horse trader Bob Allen and moving to a ranch near Ogallala, Nebraska. She still grieves for her sons who died of respiratory disease from the sod house in which Bob and she first lived, and treasures her daughters.
- Jimmy and Ben Rainey, Bill and Pete Spettle, Soupy Jones, Needle Nelson, Jasper Fant, Bert Borum, Lippy Jones, Sean and Allen O'Brien – These other hands were hired by Call to work the cattle drive.
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