A US Army cavalry unit returns from a two week patrol to find the inhabitants of a Christian mission near its home fort have been killed by Apache Indians. Among the victims is the savagely tortured wife of the patrol’s leader, Capt. Victor Kaleb (Bekim Fehmiu). Still alive after she was skinned alive, Kaleb has to execute his wife to take her our of her terminal pain.

Kaleb believes part of the fault lies with the passive fort commander, Major Wade Brown (Richard Crenna) and loudly criticises him in front of his command. Major Brown responds to Captain Kaleb by asking who was it who shot his wife, the Apaches or him? Captain Kaleb responds by shooting Major Brown in his leg and arm, then deserts the army. He disappears into the southwestern frontier to wage a private one man war of revenge against the Apache.

Two years later General Miles (John Huston) arrives at the fort with criticism of now Colonel Brown’s unsuccessful military command and an offer of pardon for Kaleb. The scouts Natchai (Ricardo Montalbán) and Tattinger (Slim Pickens), old friends of Kaleb, are sent out to entice him (and his pet wolf-dog) back to the fort. With a bit of trickery they succeed.

General Miles tells Kaleb that Apaches led by Chief Mangus Durango have gathered in Mexico, intending to cross the border and attack at any time. As the United States Army is prohibited from entering Mexico, the General, over Brown’s objections, promises Kaleb amnesty in exchange for leading a select band of soldiers in plain clothes across the border to wipe out the Apache stronghold known as “La Spina Dorsale Del Diavolo”, the Devil’s Backbone.

In a reversal of the scenario of The Dirty Dozen, the formerly wanted Kaleb has his pick of the soldiers at the fort for his mission. Those willing to go on the mission include dynamite expert Reynolds (Chuck Connors), who also is an Army Chaplain, knife-fighting expert and military prisoner Corporal Jackson (Woody Strode), Gatling gun expert Captain Robinson (Patrick Wayne), grizzled veteran Quartermaster Sergeant Schmidt (Albert Salmi) and young army Lt. Ferguson (Brandon deWilde). A blustery Englishman, Crawford (Ian Bannen), sent by the British Army to study frontier tactics is selected by Kaleb’s wolf dog. Kaleb selects the post’s surgeon Dr. Robinson (Larry Stewart). Most of the men hate Kaleb, especially Trooper O’Toole (John Alderson).

Kaleb leads them into the desert to train them for the mission. It is severe, and results in a death of one of the party. The band also encounters Apaches, who they kill. On their return to the fort, Major Brown reveals that, despite the general’s amnesty offer, he intends to arrest Kaleb for having shot him two years ago. In response the general orders Brown to accompany Kaleb on the mission. Brown cannot disobey. Natchai and Tattinger go along as well.

They cross the border and successfully infiltrate the Apache stronghold of The Devil’s Backbone by bringing their mounts and equipment up hazardous cliffs. After a successful smaller attack on part of the Apaches, due to one man’s sense of morality the rest of the Apaches are alerted leading to a fierce battle with the main body of the Apaches. Kaleb’s elite force wins, in large part due to the advantages proffered by dynamite and machine gun fire. The victorious survivors return to the fort, where an embarrassed General Miles explains that despite his amnesty offer he has been ordered to arrest Kaleb. Colonel Brown suggests the resolution: they will all say Kaleb was killed in action at the Devil’s Backbone. Kaleb mounts up and rides away from the fort back into the desert.