Arkady Kirsanov comes home from university bringing his admired friend Yevgeny Bazarov, a medical student who calls himself a nihilist. They arrive at the modest estate of Arkady's gentle, music-loving father Nikolai, who farms his land uneasily after freeing his serfs, and of Nikolai's polished, aristocratic brother Pavel. From the first meal it is clear that the older men and the young guest belong to different worlds.
Bazarov's creed is plain negation. A nihilist, Arkady explains, bows to no authority and takes no principle on faith. Bazarov trusts only natural science and usefulness: a good chemist, he says, is worth far more than any poet. He scorns art, romance, gentlemanly honour, and reverence of every kind, and he insists that the urgent work of the day is to destroy and clear the ground, not to construct. Pavel, defender of principles and tradition, clashes with him again and again.
Away from Maryino the two friends meet Anna Sergyevna Odintsov, a calm, intelligent, wealthy widow. Bazarov, who has mocked love as romantic foolery, falls into a violent passion for her, and when he finally confesses it the feeling is fierce, painful, almost like hatred. She draws back, unwilling to risk her composure, and he leaves wounded and angry with himself. Arkady, meanwhile, quietly turns from Bazarov toward Anna's younger sister Katya and a gentler, more ordinary happiness.
Bazarov goes home to his adoring, simple parents, the old army doctor Vassily and the pious Arina, whose tenderness he cannot return without embarrassment. Returning to Maryino, his needling of Pavel ends in an absurd, almost bloodless duel that exposes how little the grand quarrel has changed anyone. The strong, self-sufficient man is increasingly isolated: estranged from his disciple, rebuffed by the woman he loves, unable to live easily among either the fathers or the people he claims to serve.
Back at his parents' house, Bazarov cuts himself while dissecting a peasant dead of typhus and contracts the infection. Facing death with grim clarity, he sends for Anna, admits that Russia perhaps never needed him after all, and dies. The novel closes six months later with marriages and a fragile peace among the survivors, and then at Bazarov's village grave, where his old parents weep and the flowers speak of a reconciliation and a life without end that no theory could supply.