The book begins with V. oscillating, as he will throughout the novel, between reminiscences of Sebastian Knight the man and analyses of Sebastian's works. He introduces right away some biographical facts -- his relationship to Sebastian (they are half-brothers with the same father), the death of Sebastian's parents (his father is killed in a duel, his mother dies after abandoning the family of a heart disease) -- and some literary criticism -- a scathing dismissal of a prior biography of Sebastian written by one Mr. Goodman, Sebastian's former secretary.
V. apparently found the book difficult to begin; he tries several approaches, interviewing Sebastian's former governess, his Cambridge friends, and delving into his own memory. Each beginning leads nowhere. We learn some amusing anecdotes about Sebastian -- such as an Eastern trek with a futurist poet and his wife -- but nothing insightful. When he bogs down, V. returns to his favorite target, Mr. Goodman, whom he attacks as an greedy, parasitic ignoramus with clownish historical-philisophical methods. We do catch a glimpse of Sebastian at Cambridge. He appeared to adore England and was tortured that he could never pass as truly English. Later at Cambridge he began writing in earnest, which turned him inward and largely removed him from society.
In researching his biography of his half-brother, V. visits Mr. Goodman (before he is aware of Goodman's biography) and is brushed off. While there he meets Helen Pratt, friend of Clare Bishop's (Sebastian's long-time girlfriend), who offers to help with his researches. They later meet and Miss Pratt tells V. all she knows about Sebastian, meanwhile assuring V. that he should not meet Clare Bishop. V. tries anyway, but gives up when he sees that Clare is pregnant. He later learns that she has a miscarriage and dies giving birth.
V. intersplices his own remembrances of Sebastian with his researches. He talks of meeting Clare and Sebastian in Paris -- he found them to be very happily in love. V. continues with their tale, saying that Sebastian developed the same heart disease as his mother and that Clare acted as a nurse of sorts, also typing his books while Sebastian dictated them.
This leads V. to discuss Sebastian's novels in detail. He takes them chronologically, starting with a mock-murder story, The Prismatic Bezel, and then a love story of sorts, Success. V. also introduces P.G. Sheldon, a poet who knew Sebastian well during this period. Through Sheldon we hear of the break-up between Clare and Sebastian; Clare and he handled success differently. Eventually, Sebastian goes without Clare to Blauberg, where he meets another woman (though we learn about this later). He and Clare fizzle out. Meanwhile, Sebastian hires Mr. Goodman to handle his affairs while he works on new projects.
V., obsessed with this "other woman" in Blauberg (who he finds is Russian), goes to Blauberg and tries to wheedle her identity from the hotel manager, who refuses. Later, V. meets a former detective, Mr. Silbermann, who agrees to help with the mystery. Silbermann allows V. to narrow down the possible "other women" to four. V. visits them in turn, starting with a woman in Berlin who reminds him of his mother and thus, he feels, could not have disrupted Sebastian's happy home.
In Paris he searches for the other three, beginning with Madame de Rechnoy. He learns from this woman's husband that she is an unlikely candidate for the affair, though his first wife, a woman named Nina, fits the bill precisely. V. ignores Nina for the time being and moves on to Madame von Graun, who is out. He speaks with her friend, Madame Lecerf, instead. Lecerf entices V. and invites him to meet von Graun at her country house. V. seems certain that von Graun is the femme fatale, and he pursues this possibility only to find, due to a linguistic slip (Lecerf speaks Russian!) that Lecerf has been leading him on the whole while. She is, in fact, Nina -- and Sebastian, in fact, had his affair with her.
Once the mystery is solved it proves rather irrelevant -- and indeed seems to reveal V.'s obsessiveness more than anything about Sebastian. V. retreats to discussion of Sebastian's final novel, a book about death and dying, and remarks that the book followed from Sebastian's own experience of death. V. states that this is his favorite of Sebastian's books -- a statement that invites us to consider that V. enjoys the thought of Sebastian's death.
V. then relates the final act of his brother's life. He tells of receiving a letter from Sebastian begging him to visit in Paris. Delayed by business, V. is finally urged to visit Paris when Sebastian's doctor sends an urgent telegram. V. narrates a hellish journey, fraught with every delay imaginable, before he finally arrived at Sebastian's hospital. He bribes a nurse to allow him near Sebastian's death bed, only to learn afterward that the dying patient wasn't Sebastian at all -- Sebastian had died already. Unperturbed, V. feels a cathartic connection with his half-brother and decides that he has "become" Sebastian Knight because he has understood Sebastian's soul. Thus he embarks on the writing of the "biography" (or is it a confession? or something utterly different?) we have just completed reading.