The initial uprising occurred amid general Chinese-Tibetan tensions and in a context of confusion, as Tibetan protestors feared that the Chinese government might arrest the 14th Dalai Lama. The protests were also fuelled by anti-Chinese sentiment and separatism. At first, the uprising consisted of mostly peaceful protests, but clashes quickly erupted and the Chinese People's Liberation Army (PLA) eventually used force to put down the protestors, some of whom had captured arms. The last stages of the uprising included heavy fighting, with high civilian and military losses. The 14th Dalai Lama escaped from Lhasa, while the city was fully retaken by Chinese security forces on 23 March 1959. Thousands were killed during the 1959 uprising, although the exact number is disputed.

Earlier in 1956, armed conflict between Tibetan guerrillas and the PLA started in the Kham and Amdo regions, which had been subjected to socialist reform. The guerrilla warfare later spread to other areas of Tibet and lasted through 1962.