At the beginning of the novel we find Nikolai Petrovich Kirsanov waiting at a posting station with his valet Pyotr for the return of his young son Arcady, who is coming home from Petersburg where he has recently completed his degree. While Nikolai sits waiting the reader is introduced to his circumstances. We are told how he is the son of a half-literate general who had served in the war against Napoleon in 1812 but spent most of his life in the provinces, and of a strong mother of the type of "commanding matrons". Nikolai, following an education by ineffective governors is prevented from taking up his commission in the army by injury, is allowed to take up a civilian post by his father. At eighteen he entered the Petersburg university and took his degree in 1835, the same year in which his father and mother died. As soon as the mourning period was over he married the daughter of his former landlord, "a pretty and, as they say 'cultured' girl, who was addicted to reading serious articles in the Science section of the Gazettes." Shortly thereafter they moved to his country home, where their son Arcady was born. In 1847 his wife died, the shock almost killing him, and in 1855 he accompanied Arcady when he went to university in Petersburg, staying with him for three years before returning for the winter of 1858-9. It is thus that we find him waiting for his son in May, 1859. The timing of the novel is important as its action coincides with the period in which Turgenev himself freed his serfs, and in which the oncoming emancipation of the serfs was becoming increasingly obvious and the arguments for and against were becoming an increasingly important part of the Russian public consciousness, and the publication of the work in 1862 followed just one year after the signing of the Emancipation Act by Alexander II in February 1861.
When Arcady does arrive at the posting station he brings with him one of his fellow students, Yevgeny Vassilich Bazarov. They then return in the company of Nikolai Petrovich and his valet, Pyotr, who Turgenev describes ironically as "a representative of a modern and more perfect age", to Arcady's father's rather chaotically run estate; the problems of which reflect to a great degree those experienced by Turgenev himself in the running of his own estates, especially as Nikolai, like Turgenev has freed his serfs. Arcady and Bazarov both stay for a while on the Kirsanov's estate. Here Bazarov, who declares himself to be a "nihilist", and who becomes the hero of the novel, occupies himself with early morning walks in search of specimens for dissection and examination later in the day in preparation for the medical examinations which he intends to take in the following year, while Arcady spends his time in idleness. Here on the estate the reader is also introduced to two more important characters; Arcady's uncle Pavel Petrovich and the young peasant-girl Fenichka who is Nikolai's lover and who has borne him a baby son. Pavel Petrovich is a foppish, intolerant and laconic Anglophile who has led a frustrated and pointless life and been disappointed and disillusioned by his unsuccessful love for a woman whom he followed everywhere much in the same way that Turgenev followed Pauline Viardot. It is his arguments with Bazarov which illuminate the conflict between the two generations, that is, between the "new men and women" as exemplified by Bazarov, and the brothers Kirsanov and everything that they stand for, or to put it yet another way, between the fathers and sons. Fenichka, a young girl of only twenty-three entrusted to Nilkolai's care after the death of her innkeeper mother from cholera, is naturally uncertain of how to behave in the company of the members of the Kirsanov family as she is of a lower social standing, and while she is the mother of Nikolai's child she is not his wife. She is particularly nervous of Pavel, but he does make efforts to show her his goodwill, even though he does so with obvious discomfort. Likewise, Arcady, who believes that his father should marry Fenichka and validate their union, does not make her feel comfortable, and it is in fact only Bazarov with whom she seems truly at ease, and once she discovers that he has medical knowledge she is even happy to have him woken during the night to have him check on her baby.
Life continues at the estate at Maryino with Arcady living the life of a "true sybarite" and Bazarov going on with his studies, while all the time the animosity between the latter and Pavel Petrovich heightens, and Nikolai becomes more and more enervated by Bazarov's scathing attitude towards his old-fashioned ways. Then a message arrives from one of Nikolai's late wife's relations, a certain Matvey Ilyich Kolyazin, who has arrived in the provincial capital to inspect the area in his official capacity and invites Pavel, Nikolai and Arcady to come and stay with him at his lodgings in town. That same evening what Turgnev calls the "battle royal" takes place between Bazarov and Pavel. That is, an animated argument takes place between them at tea during the course of which Bazarov sneers at Pavel's beliefs in the aristocracy, liberalism, progress, principles, art and the emancipation of the serfs, calling them "a lot of foreign - and useless - words!" Pavel is totally baffled by Bazarov's nihilism and despises him, while Bazarov in turn sneers at him and what he stands for.
The day after this argument takes place Arcady and Bazarov, on the suggestion of the latter, leave for the town on the pretext of accepting the invitation of Matvey Ilyich Kolyazin. Matvey Ilyich, an unintelligent but "modern" official with an extraordinarily high self-opinion advises Arcady that he should pay a visit to the governor, who is holding a large ball for him. Arcady and Bazarov duly go to pay their respects to the governor, who in turn invites them to the ball. Returning to their lodgings they encounter an old acquaintance of Arcady's, a bizarre and foolish character named Sitnikov who persuades them to join him in a visit to the house of Eudoxia Kukshina, a tireless name-dropper who revels in her ability to include the ideas of the most current international thinkers in her every utterance. Perhaps her most important role however is that she brings Madame Odintzova into the story, describing her as the only good-looking woman she knows in the town who is not "light-headed", and saying how she too will be attending the governor's ball; a fact that, unusually, captures Bazarov's attention.
A few days later, at the ball, Arcady meets, dances with and talks to the twenty-nine year old Anna Sergeyevna Odintzova, by whom he is evidently quite taken, believing her to be quite beautiful, and moreover, a lady of the world. The next day, on her invitation, Bazarov and Arcady pay a visit to Odintzova's hotel. We discover at this point that Odintzova (nee Loktyeva) is the daughter of a speculator and gambler, who on his death left her rather impoverished. She then married a rich and much older man named Odintzov who on his death six years later left her his entire fortune, and at the point at which we find her now she lives with her sister and aunt in some luxury at her favourite estate at Nicolskoye, some thirty miles from the town. For once Bazarov is impressed by someone and is even somewhat nervous in her presence, and at the end of their meeting Odintzova extends an invitation to both of them to visit her at her estate, which they decide to do in two days' time.
At Odintzova's estate they meet her younger sister, Katya, a charming but far less self-assured young lady than her sister, and also Princess K., Odintzova's ageing and cantankerous aunt. That evening Odintzova, Bazarov and a local gentleman, Porfiry Platonich play cards together, while Katya plays the piano for Arcady. We are then told how later that evening Odintzova thinks of the liking she has taken to Bazarov and how she has never fallen in love.
The next two weeks are passed over very quickly as the well-ordered pattern of life on the Odintzova estate goes on, with Arcady spending most of his time with Katya and Bazarov with Odintzova. However, Bazarov has become anxious and thrown off balance by Odintzova's obvious favour of him, while Arcady has decided that he is in love with Katya, a thought that occasionally besets him with bouts of depression. Then Timofeyich, the steward of Bazarov's father's estate, appears to remind Bazarov of his duty to return home and see his parents. Bazarov and Odintzova have a dispute about the perfectly ordered nature of her life. Then the next day he declares to Odintzova that he loves her; a declaration that she, scared of a possible disruption of her ordered life, does not return, claiming that Bazarov has "misunderstood" her. The next day Arcady and Bazarov leave for the latter's family estate, where they meet Bazarov's doting parents, who are quite baffled by their son's lack of affection and snooty attitude towards their simple ways. We soon see that Bazarov's parents have none of the world-weariness or modern ideas of their son, but are instead honest, old-fashioned people who desire nothing more than the simple pleasures of life and to make their only son happy. Bazarov meanwhile becomes increasingly uneasy and his relationship with Arcady starts to show the strain, especially when Bazarov suggests that perhaps it would not be bad if they let one of their discussions lead to a real fight, an event only averted by the timely arrival of Vassily Ivanich, Bazarov's father.
Bazarov soon decides to leave again, and he and Arcady depart once more for the latter's estate at Maryino and on the way stop off at Nicolskoye to see Odintzova and Katya. The visit is a failure: Katya is ill and does not come downstairs and the conversation with Odintzova is stilted and after four hours she complains of an attack of spleen and they take their leave. They are then received well back at Maryino where all has been going far from well on the estate for Nikolai, who has been having great trouble with his peasants, who are not paying their rent and arguing over land divisions. Over the next ten days Bazarov returns to his dissections, while Arcady finds his mind constantly straying back to Katya and Nicolskoye. He then returns to Nicolskoye, taking with him letters that were once written to his late mother by Anna, Odintzova's mother.
Meanwhile, at Maryino, Bazarov and Pavel mainly avoid arguments with each other, although the animosity between them remains undiminished, but soon Pavel catches Bazarov stealing a kiss from Fenichka, which sends him into a rage and he challenges him to a duel. Pavel misses and Bazarov wounds him in the leg. The next day Bazarov leaves and soon after Pavel having assured himself that Fenichka does love his brother, implores him to marry her, which he agrees to do.
Back at Nicolskoye Arcady's romance with Katya continues innocently. Then Bazarov reappears and the next day Arcady declares his love to Katya and asks for her hand inmarriage, which she gives. The next day, Bazarov once again leaves for his estate where he is joyfully received by his parents. However, he soon slips into depressed apathy and while performing an autopsy on a typhoid victim, cuts and infects his finger, and the infection soon spreads to the rest of his body and his impending death becomes obvious. He sends a message to Odintzova who arrives with her own doctor, but it is too late and he dies alone with her.
The action of the final chapter of the novel takes place six months later in January of 1860. The marriages of Arcady and Katya and Nikolai and Fenichka have taken place two weeks previously in the parish church and a farewell dinner is now being held for Pavel, who is setting off for Moscow on business. In the last paragraphs Turgenev then tells the reader what has happened to his characters now, and we learn that Odintzova has remarried a lawyer, Princess K. has died, both Arcady and Nikolai have settled down at Maryino, where the former has become passionately involved in the running of the estate. Katya has given birth to a son, while Fenichka's son, Mitya is already growing up. Pavel, meanwhile, has relocated to Dresden, where he spends most of his time with Russian and English visitors. We also learn that Madame Kukshina is in Germany too, studying at Heidelberg, while Sitnikov continues to gad about St. Petersburg.
The very last paragraph of the book, however, is less cheerful in tone, and depicts the pristine grave of Bazarov, which stands in the midst of a derelict churchyard often visited by his bowed and destroyed parents, who can scarcely tear themselves from their prayers at their son's graveside.