The first death, from which everything else in The Human Beast proceeds, is that of Grandmorin, the elderly railway executive. Roubaud has discovered that his wife, Séverine, had, as a young girl, been forced into a relationship with Grandmorin. Though it obviously wasn't her fault, the abusive, brutal Roubaud beats her up, then drags her onto the train where Grandmorin has fallen for a ruse to meet Séverine. Roubaud stabs Grandmorin to death. Later, Jacques Lantier, a railway driver, and Séverine begin a relationship, despite Jacques having a psychopathic history of wanting to kill women to whom he feels attracted.
Aunt Phasie is Jacques's cousin and godmother. She is also the mother of the tomboyish Flore, who is desperately in love with Jacques, though he ignores her. Both Flore and her father, Misard, work for the railway at a remote signal station. After Aunt Phasie has died, Flore, out of mad jealousy, perpetrates a sabotage on the railway in the hope of causing a train wreck to kill both Jacques and Séverine. Others are killed, but they survive. Distraught with regret and self-hatred, Flore herself is the next to die, committing suicide by throwing herself in front of a train.
Though Jacques and Séverine have intended to murder Roubaud both in revenge for what Roubaud has done to her and simply to free her from her marriage to him, it is Jacques who finally succumbs to his sociopathic illness and stabs Séverine to death. Ironically Roubaud, though perhaps more deserving of death than anyone, survives but is sent to prison for life.
The final deaths are those of Jacques and the fireman on his train, Pecqueux. On an express train transporting French soldiers to the front for the Franco-Prussian War, Pecqueux attacks Jacques in a jealous rage after having over-stoked the engine. The two men kill each other, and the train hurtles forward at top speed, out of control and without a driver. The final deaths, we are led to believe, will be those of the soldiers crammed into cattle-car transports and madly getting drunk, either in the inevitable wreck of the train or at the battle front, in which France is to be defeated.