The Bedwetters, a group of misfits at the Box Canyon Box Camp, have a mission that provides the basis of the plot of Bless the Beasts and Children. Their mission is to rescue the buffalo from their deaths and to escape from the oppressive camp environment. The book opens with John Cotton's dream, in which he and his fellow cabin mates become the victims of a shooting very similar to the buffalo killing that he has witnessed the previous day, at the Arizona Game and Fish Department's annual three-day "hunt." After their visit to the buffalo preserve, the boys had remained sickened by the memory. Cotton awakens to realize that Lally two has run away, and, upon finding him, the boys unanimously support escaping for the night on a mission to rescue the buffalo from their gruesome deaths. After packing for their adventure, they futilely attempt to roll a car out to the road. Spotting the camp director outside his cabin, the boys stiffen with fright, but pass unnoticed.
The boys mount horses from the camp, and exiting the camp gates in pride at their boldness. Filled with excitement and anticipation, they gallop down the road. As cars pass them in the night, Cotton recognizes their high visibility and their need for a vehicle of some sort. Abandoning the horses, they travel by foot into Prescott. After failed attempts to steal cars from a hotel parking lot and a used car lot, they finally succeed in hotwiring an old Chevy parked next to a body shop. Piling into the pickup, all but Teft, the driver, keep low and out of sight as they reach the open expanse outside of Prescott. Cotton contemplates their adventure, and the potential respect it might win the boys within the camp if they succeed. At the top of Mingus Mountain, the boys awake to see Flagstaff in the distance.
When the Bedwetters stop in Flagstaff to pick up some dinner at an all-night bar and restaurant, two bowlers hassle and interrogate them. Their jumbled accounts force Cotton to tell the truth and to urge the boys to head out to the car without waiting for their food. When they realize that the bowlers have followed them, they pull over, and Teft responds to their threats by aiming the rifle straight at them, and turning to shoot and puncture one of their tires. The bowlers retreat to their car and the Bedwetters resume their journey. In the last few miles before their destination, the engine sputters and dies because the truck has run out of gas. They must decide whether to continue with their mission or return home immediately, and the group votes to continue. The Bedwetters arrive at the buffalo preserve, where in the darkness they slip on a pool of blood, and then rinse off in a nearby pond. In their effort to understand the layout of the pens, they all scale the catwalk. After a few frustrating attempts to liberate the buffalo, they throw their flashlights, radios, and hats to encourage the buffalo in the right direction, and watch them run free.
Ecstatic about their accomplishment, the Bedwetters celebrate the buffalo's newfound freedom by sharing three bottles of airline whiskey. They soon realize, however, that more work lies ahead of them. The buffalo have remained nearby rather than dispersing out into the fields. Teft takes the wheel of the "Judas truck," and the rest of the boys feed hay to the buffalo from the back of the truck, luring them toward Mogollon Rim and contemplating the significance of their rescue of the buffalo. When Teft notices a fence barring their path, Cotton futilely attempts to break through it. Spotting a Jeep and two pick-ups in the distance, he orders Teft to use his rifle to shoot at them and takes the wheel of the truck himself, despite his inability to drive. He steps on the accelerator and succeeds in breaking the fence, laying on the horn long and loud to startle the buffalo toward the other side of the fence. Somehow unable to locate the brakes, Cotton crashes to his death. Approached by the sportsmen and officials, the five boys experience both grief and pride over Cotton's death.