The novel begins with an overview of the main character's background. Louis Lambert, the only child of a tanner and his wife, is born in 1797 and begins reading at an early age. In 1811 he meets the real-life Swiss author Madame de Staël (1766–1817), who – struck by his intellect – pays for him to enroll in the Collège de Vendôme. There he meets the narrator, a classmate named "the Poet" who later identifies himself in the text as Balzac; they quickly become friends. Shunned by the other students and berated by teachers for not paying attention, the boys bond through discussions of philosophy and mysticism.
After completing an essay entitled Traité de la Volonté ("Treatise on the Will"), Lambert is horrified when a teacher confiscates it, calls it "rubbish", and – the narrator speculates – sells it to a local grocer. Soon afterwards, a serious illness forces the narrator to leave the school. In 1815, Lambert graduates at the age of eighteen and lives for three years in Paris. After returning to his uncle's home in Blois, he meets a woman named Pauline de Villenoix and falls passionately in love with her. On the day before their wedding, however, he suffers a mental breakdown and attempts to castrate himself.
Declared "incurable" by doctors, Lambert is ordered into solitude and rest. Pauline takes him to her family's château, where he lives in a near coma. The narrator, ignorant of these events, meets Lambert's uncle by chance, and is given a series of letters. Written by Lambert while in Paris and Blois, they continue his philosophical musings and describe his love for Pauline. The narrator visits his old friend at the Villenoix château, where the decrepit Lambert says only: "The angels are white." Pauline shares a series of statements her lover had dictated, and Lambert dies on 25 September 1824 at the age of twenty-eight.