After serving in the army, Captain Buck Devlin and the cavalry troopers Sergeant John Maitland and Private Wilbur Clegg decide to settle down at Devlin’s brother’s homestead. Upon arrival, they narrowly escape a Native American attack, but unfortunately, they arrive too late to save Devlin’s brother, who is killed by faulty ammunition that explodes during a confrontation. Driven by grief and a desire for justice, the three men set out for Medicine Bend to uncover who supplied the defective ammunition. Along the way, they receive generous aid from the local community, who also lend them their funds to buy much-needed supplies for their journey.
However, their troubles continue when they are robbed of everything — their money, horses, and even their uniforms — by unknown culprits. Luckily, they stumble upon a group of Brethren (in Christ), who have also been victims of theft. The townspeople generously provide the travelers with spare clothing, prompting Devlin to adopt the guise of a Brethren to blend into the town without raising suspicion. As they investigate, they quickly uncover that the corruption and theft are orchestrated by Ep Clark, a man who controls the town’s authorities, including the mayor and sheriff. Clark’s gang Mon actively preys on pioneers heading west, forcing honest traders out of business and stealing from travelers.
Devlin, Maitland, and Clegg go undercover to gather evidence against Clark's illicit activities. Maitland and Clegg get jobs at Clark’s store, while Devlin aligns himself with a rival merchant, Elam King, and his resourceful niece Priscilla. As Devlin gains their trust, he learns about a secret wagon train of supplies, including weapons, coming from St. Louis, which King has guarded carefully. Devlin begins night-time raids to reclaim stolen goods, including a sentimental keepsake — Nell Garrison’s brooch, which was stolen during one such theft, and which Nell is reluctant to part with.
Tensions rise when Clark becomes suspicious of the three newcomers. He attempts to trap Devlin, resulting in a shootout where one of Clark’s gang members is killed. Clark retaliates by having the sheriff arrest Maitland and Clegg for the murder, and they are swiftly sentenced to hang. Fortunately, Nell Garrison, who has taken a liking to Maitland, successfully persuades Sheriff Bob Massey to show mercy. Her plea leads to the prisoners’ release, but tragically, the sheriff is shot in the back by one of Clark’s men in the process. Brother Abraham, a respected leader of the local Brethren congregation, intervenes and helps to prevent the hanging, ensuring Maitland and Clegg are saved.
As the story reaches its climax, Devlin confronts Clark. A fierce fight ensues—highlighting the film’s title, "It's a Mad, Mad, Mad, Mad World"—with Devlin briefly knocked unconscious during the chaos. Clark attempts to kill Devlin using the defective ammunition that had previously cost Devlin’s brother his life, but Devlin fights back. When Clark grabs a scythe in desperation, Devlin pushes him down, fatally impaling him.
In the aftermath, Devlin and Maitland prepare to head off into the sunset, accompanied by Priscilla and Nell respectively. Meanwhile, Clegg surprises everyone by choosing to stay behind and serve a "hitch" with the Brethren, finding his place in the community. Throughout the film, themes of justice, loyalty, and redemption are explored amidst the wilderness and chaos, creating an action-packed story about courage and perseverance in the face of corruption and adversity.
