Jack Burns (Kirk Douglas) is an itinerant ranch hand who still lives the life of an Old West cowboy in 1960s New Mexico, shunning all modern technology, riding everywhere on his horse Whiskey, sleeping wherever he ends up in the evening, and refusing to carry any form of identification. As the film opens, Jack visits Jerry Bondi (Gena Rowlands), the wife of his friend Paul (Michael Kane), who has been jailed for aiding illegal immigrants, and vents his spleen about modern society's emphasis on telling people where they can or can't go and what they can or can't do.
Jack decides to break Paul out of jail and gets himself arrested, but Paul is near the end of his sentence and would rather serve it out and return to his family, so Jack breaks out by himself. He heads for the Mexican border, pursued by Duke City Sheriff Morey Johnson (Walter Matthau) and his deputies, the brutish Gutierrez (George Kennedy) and the none-too-bright Harry (William Schallert). Although the odds seem stacked against him, Jack manages to give them the slip, but as he attempts to cross Highway 66 in Tijeras Canyon, he finds that the modern world is about to catch up with him...
Douglas later named Lonely Are the Brave his favourite among his own films. It also provides the first film role for Bill Bixby, who makes an uncredited appearance as a helicopter pilot, and one of the first film roles for Carroll O'Connor, who plays 18-wheeler driver Hinton.
- Bar Brawl: Jack goes into a bar, where a one-armed man takes an almost instant dislike to him. Needing to get into prison to break Paul out, Jack allows the man to provoke him into a fight, and uses one arm himself to keep things fair.
- Chekhov's Gunman: Early in the film, we are introduced to Hinton, a truck driver transporting 156 porcelain toilets (or "privies" as he describes them) from Missouri to New Mexico. He appears in a few further cutaway scenes, but his importance to the plot only becomes clear in the film's final sequence, when his 18-wheeler strikes Jack as he tries to cross Highway 66 on horseback in a downpour, dealing a literal and figurative blow from the modern world that Jack has stubbornly refused to join all his life.
- Clueless Deputy: Many of Johnson's men are a bit lazy, slow on the uptake and inexperienced with real trouble.
- Get into Jail Free: In order to break Paul out of prison, Jack has to get into prison. He allows himself to be provoked into a Bar Brawl by an aggressive one-armed man, but when the police decide to let him go, he attacks one of them and is slapped with a potential one-year sentence.
- Mercy Kill: After Hinton hits Jack and Whiskey with his truck, passing motorists stop to assist, and one of them wonders aloud when someone will put Whiskey out of her misery. Johnson asks his deputy to do just that, and we hear a shot offscreen.
- The Millstone: Jack's horse Whiskey, who makes Jack more visible to his searchers, also makes it harder for him to climb over the mountain and is generally disobedient and always moving around or stopping at the wrong times. She does let Jack outrun his pursuers at one point though.
- Never My Fault: A local Air Force general volunteers some men and a helicopter for the search out of the blue to get his men a little experience. When the chopper ends up badly damaged as a result, he immediately starts blaming Johnson for it.
- Number Two: Harry is Johnson's primary deputy and confidant.
- Oh, Crap!: In the film's climax, Hinton is struggling to see through the rain as he drives his 18-wheeler down Highway 66, and when he sees Jack and the rearing Whiskey in his headlights, he gets a horrified expression as he knows he has no way to stop in time. He exclaims "Oh my God!" and pulls on the cord for his truck's horn in a last-ditch attempt to clear the road.
- Twilight of the Old West: Jack still rides everywhere on horseback and sleeps wherever he ends up in the evening; he refuses to join modern society, claiming that he resents its emphasis on telling people where they can or can't go and what they can or can't do. His Old West lifestyle, however, has been growing increasingly difficult to maintain. The tone of the film is set by the first scene, when he and Whiskey see the tracks of an aeroplane flying overhead, and Jack says they'd better make tracks as well.
- Unusually Uninteresting Sight: As Jack gets into a fight with several deputies and they thrash around on the floor, the desk sergeant just ignores them while casually typing up an inventory of Jack's (somewhat bizarre) assortment of personal effects.
- Verbal Tic: Johnson's deputy, Harry, has a habit of repeating a key word or several words from any order or rhetorical question from his boss as if it were a question, followed by "Right!" Johnson tells him several times to knock it off, but to no avail.
- Wardens Are Evil: Gutierrez the jail guard is a quick-fisted bully and the only deputy to really receive a negative portrayal in the film.
- Worthy Opponent: Jack spends most of the second half of the film being pursued by the police of Duke City. Johnson finds himself admiring Jack's tenacity, not just in somehow avoiding the every attempt by his men to bring him to justice, but in continuing to live the life of an Old West cowboy in 1962, refusing to let anyone or anything tie him down; the fact that Burns is a Korean War veteran who received the Purple Heart deepens his respect. In the final scene, after Jack is hit by an 18-wheeler, Johnson finally sees Burns up close for the first time and is asked if he is the man they have been pursuing; Johnson feigns uncertainty.
- With My Hands Tied: Subverted; Jack provokes a Bar Brawl, but has second thoughts when the man he's antagonizing turns out to only have one arm. To make things fair, he declares he'll fight with one arm held behind his back. As he's not used to fighting in this manner, he gets his ass kicked.