As well as being the most influential spiritual leader of Tibetan Buddhism, the Dalai Lama traditionally claims to be Tibet's Head of State and most important political ruler. At the age of fifteen, faced with possible conflict with the Chinese, Tenzin Gyatso was on November 17, 1950, enthroned as the temporal leader of Tibet; however, he was only able to govern for a brief time. In October of that year, a People's Republic of China army entered territory controlled by the Tibetan administration, easily breaking through the Tibetan defenders.

The People's Liberation Army stopped short of the old border between Tibet and Xikang and demanded negotiations. The Dalai Lama sent a delegation to Beijing, and, although he has rejected the subsequent Seventeen Point Agreement for the Peaceful Liberation of Tibet, he did in fact work with the Chinese government until 1959. The Dalai Lama fled to Dharamsala, India, on March 17 of that year, entering India on March 31 during the Tibetan uprising.

Tenzin Gyatso is the first Dalai Lama to travel to the West, where he has helped to spread Buddhism.

In 1989, Tenzin Gyatso was awarded the Nobel Peace Prize, the chairman of the Nobel committee saying that this was "in part a tribute to the memory of Mahatma Gandhi".