On November 17, 1950, His Holiness was called upon to assume full political power (head of the State and Government) after some 80,000 Peoples Liberation Army soldiers invaded Tibet. In 1954, he went to Beijing to talk peace with Mao Tse-tung and other Chinese leaders, including Chou En-lai and Deng Xiaoping. In 1956, while visiting India to attend the 2500th Buddha Jayanti Anniversary, he had a series of meetings with Prime Minister Nehru and Premier Chou about deteriorating conditions in Tibet.

His efforts to bring about a peaceful solution to Sino-Tibetan conflict were thwarted by Bejing's ruthless policy in Eastern Tibet, which ignited a popular uprising and resistance. This resistance movement spread to other parts of the country. On 10 March 1959 the capital of Tibet, Lhasa, exploded with the largest demonstration in Tibetan history, calling on China to leave Tibet and reaffirming Tibet's independence. The Tibetan National Uprising was brutally crushed by the Chinese army. His Holiness escaped to India where he was given political asylum. Some 80,000 Tibetan refugees followed His Holiness into exile. Today, there are more than 120,000 Tibetan in exile. Since 1960, he has resided in Dharamsala, India, known as 'Little Lhasa', the seat of the Tibetan Government-in-exile.