Palade was born at Iasi in Romania. Educated at Bucharest University, where he was professor of physiology during World War II, he emigrated to America in 1946, becoming a naturalized citizen in 1952. He worked at the Rockefeller Institute for Medical Research, New York, becoming professor of cytology there (1958–72). In 1972 he became director of studies in cell biology at Yale University's medical school. In 1990 he was appointed dean of scientific affairs at the University of California at San Diego. He retired in 2001.

Palade's work was primarily concerned with studies of the fine structure of animal cells, although he also investigated the nature of plant chloroplasts. He showed that minute semisolid structures in cells, known as mitochondria, have an enzymic effect, oxidizing fats and sugars and releasing energy. His discovery of even smaller bodies called microsomes, which function independently of the mitochondria (of which they were previously thought to be part), showed them to be rich in ribonucleic acid (RNA) and therefore the site of protein manufacture. The microsomes were subsequently renamed ribosomes. For his work in cellular biology, Palade received, with Albert Claude and Christian de Duve, the Nobel Prize for physiology or medicine (1974).