Pramoedya, the son of a schoolteacher, went to Jakarta while a teenager and worked as a typist there under the Japanese occupation during World War II. When the Indonesian revolt against renewed Dutch colonial rule broke out in 1945, he joined the nationalists, working in radio and producing an Indonesian-language magazine before he was arrested by the Dutch authorities in 1947. He wrote his first published novel, Perburuan (1950; The Fugitive), during a two-year term in a Dutch prison camp (1947–49). This work describes the flight of an anti-Japanese rebel back to his home in Java.

After Indonesia gained independence in 1949, Pramoedya produced a stream of novels and short stories that established his reputation. The novel Keluarga gerilja (1950; “Guerrilla Family”) chronicles the tragic consequences of divided political sympathies in a Javanese family during the Indonesian Revolution against Dutch rule, while Mereka jang dilumpuhkan (1951; “The Paralyzed”) depicts the odd assortment of inmates Pramoedya became acquainted with in the Dutch prison camp. The short stories collected in Subuh (1950; “Dawn”) and Pertjikan revolusi (1950; “Sparks of Revolution”) are set during the Indonesian Revolution, while those in Tjerita dari Blora (1952; “Tales of Bora”) depict Javanese provincial life in the period of Dutch rule. The sketches in Tjerita dari Djakarta (1957; “Tales of Jakarta”) examine the strains and injustices Pramoedya perceived within Indonesian society after independence had been achieved. In these early works Pramoedya evolved a rich prose style that incorporates Javanese everyday speech and images from classical Javanese culture.

By the late 1950s Pramoedya had become sympathetic toward the Indonesian Communist Party, and after 1958 he abandoned fiction for essays and cultural criticism that reflect a left-wing viewpoint. By 1962 he had become closely aligned with communist-sponsored cultural groups. As a result, he was jailed by the army in the course of its bloody suppression of a communist coup in 1965. During his imprisonment he wrote a series of four historical novels that further enhanced his reputation. Two of these, Bumi manusia (1980; This Earth of Mankind) and Anak semua bangsa (1980; Child of All Nations), met with great critical and popular acclaim in Indonesia after their publication, but the government subsequently banned them from circulation, and the last two volumes of the tetralogy, Jejak langkah (1985; Footsteps) and Rumah kaca (1988; House of Glass), had to be published abroad. These late works comprehensively depict Javanese society under Dutch colonial rule in the early 20th century. In contrast to Pramoedya's earlier works, they are written in a plain, fast-paced narrative style.

Following his release from prison in 1979, Pramoedya was kept under house arrest in Jakarta until 1992. The autobiography Nyanyi sunyi seorang bisu (The Mute's Soliloquy) was published in 1995.