The Four Horsemen of the Apocalypse follows several members of a multi-cultural family, as World War I wages on around them. The novel begins in the days leading up to the war, introducing the Desnoyers family. The Desnoyers include the father, a retired rancher, his Argentinean wife, and their two children, son Julio and daughter Chichi. Also introduced are the family's German cousins. As the war begins, the family cannot believe that such a war can be bad for their family or their country. However, as the war continues, and they suffer many losses, the family quickly learns that war is not an affair to be taken lightly. The Four Horsemen of the Apocalypse is a timeless story about family, love and loss that will continue to be enjoyed for decades to come.

Julio Desnoyers waits in the garden of Chapelle Expiatoire for his lover to meet him. Julio has just returned from a trip to Argentina in order to raise money for his impending marriage. While he has been gone, talk of war with Germany has increased. On his journey home, Julio traveled on a German ship. On board ship, the captain at first went out of his way to make all the French citizens feel comfortable. However, when news of the tensions between the two countries increased, the German captain and his crew members became increasingly hostile. Now, Julio watches as the people around him are reading more about these tensions in the evening papers. When Julio's love finally joins him, he becomes concerned about what these rumors of war will do to their impending marriage.

Julio's father is a French citizen who ran away from the conflict of 1870, traveling to Argentina rather than be a soldier in his home country's military. While searching for ways to become a rich man, Julio becomes employed by a local rancher. This rancher has no legitimate sons, so he takes Marcelo under his wing. Marcelo works as foreman on the ranch, putting up with his boss's hot temper and unusual generous nature in hopes of one day running the entire ranch. While being treated as a member of the family, Marcelo falls in love with the owner's oldest daughter. They marry. Soon after, the boss brings in a German accountant to help Marcelo oversee the books for the ranch. The boss's youngest daughter falls in love with the German and runs away with him, when the boss forbids their love. Soon, they return to the ranch and reside under Marcelo's protection from the boss. Grandchildren begin to fill the ranch, with Marcelo's children becoming the light of the old rancher's day, especially his son who is named after the old rancher. When the rancher dies, the majority of the estate goes to Marcelo and his wife. Soon after, the German brother-in-law sells his inheritance and returns to Germany with his family. Marcelo retires and moves his family to Buenos Aires.

After a short time, Marcelo's family becomes envious of the letters they receive from their aunt in Germany and suggest to Marcelo that they follow suit and move to Marcelo's native France. Soon Marcelo is infected with this same enthusiasm and prepares to move his family to Paris. Once there, Marcelo indulges in antique collecting, scouring many sources in order to find the best bargains. Soon the large apartment he has rented for his family in Paris is overcrowded. Marcelo finds a good deal on castle in the country and buys it, furnishing it with all the bargain antiques he can find. Julio, in the time being, decides he wants to be a painter. The family buys him a studio in the city where Julio, instead of spending his time painting, spends his time drinking in the salons and waging honor battles. When Julio becomes a tango teacher and becomes the lover of a married woman, Marcelo washes his hands of the young man, outraged at his son's dishonorable behavior.

When war is declared, the family can only watch as other men are called to war. Julio is exempt from becoming a soldier since he is not a French citizen. However, his lover's husband and brother are called to duty. Soon all she can think of is the loneliness in which she watched her husband go to war. The lover becomes a nurse in order to help with the war effort. Soon after this, rumors begin that the German military is on its way to Germany. Marcelo sends his wife and daughter to the South while he goes to protect his precious antiques in his country castle. Julio's lover leaves town as well and he goes after her.

Marcelo arrives in the country just as the French retreat through the small village where his castle lies. Soon after the German's arrive, commandeering his castle for their general's headquarters. Marcelo is forced to sit idly by while the residents of the village are killed in cold blood and his castle is emptied of all its valuables. Soon after, the caretaker is murdered and his daughter raped. The next day, the general and his men move toward the battle taking place just on the other side of the river. More Germans come, using the castle as a hospital for the wounded. Once again, Marcelo is forced to sit idly by while they dig graves in his gardens to bury their dead. However, the battle turns, and the Germans retreat. The castle is destroyed as the French push the Germans even further, once again taking control of the tiny village.

During Marcelo's adventures, Julio searches for and finds his lover. Her husband has been wounded in a battle and she has come to care for him. Julio is heartbroken when she tells him that she still loves her husband despite her love for Julio and she plans to stay with him. Julio offers to become a soldier like her husband, but the lover refuses to waver in her decision. Julio joins the war effort anyway, stopping Paris only long enough to say farewell to his father.

In Julio's absence, his parents become frequent visitors to his studio where a friend has taken up residence. Marcelo becomes such a frequent visitor that the friend is overwhelmed by his presence. A senator friend of Marcelo's, to whose son his daughter is engaged, arranges for himself and Marcelo to go to the war front in order to visit their son's. The trip is dangerous and uncomfortable, but Marcelo is given the chance to see his son in the trenches and to realize that his son has now become a man. Shortly afterward, the senator's son is wounded and returns home. There is a quiet wedding after his wounds heal. During this time, Julio is also wounded in a face to face battle with a German captain who turns out to be the same captain who was on the boat Julio took from Argentina months before. After Julio returns to the front, his mother fears the worst. Soon after, word comes to the family that Julio has been killed in battle. The family goes to the battle site in order to visit his grave, the elder Desnoyers regretting their move to Paris and looking forward to their own deaths. Their daughter, at the same time, feels deep relief that her husband is not one of the fallen and looks forward to their future together.