Following the Xinhai Revolution and the collapse of the Qing dynasty, the section was replaced by Mongolian and Tibetan Affairs Agency under the Ministry of the Interior in April 1912.

[3] After the Communist revolution in 1949, and the central government of China's relocation to Taiwan, formerly a Qing province turned colony that was acquired from Japan in 1945 after the end of World War II, the MTAC ceased its activities in Tibet and Mongolia, although it served as a governmental body which assisted in the relationship between ethnic Mongols and Tibetans in Taiwan and increasing the communication between the Taiwanese and the Mongols as well as the Tibetans.

From 1971 to 1978, the MTAC also recruited ethnic Tibetan children from India and Nepal to study in Taiwan, with the expectation that they would work for a ROC government that returned to the mainland.

On 14 August 2017, the Executive Yuan, now led by the independence minded Democratic Progressive Party (DPP) administration, announced that the MTAC would be dissolved by the end of the year.

The center was established in 1993 in the former residence of the Changkya Khutukhtu, Lobsang Pelden Tenpe Dronme, who fled to Taiwan after the Chinese Civil War in 1949.