The Chamdo Prefecture was called "Kam" or "Kham" in ancient times so that it could be differentiated from the U, Tsang and Ngari prefectures. The Karub and Lessor Enda relics found respectively in 1977 and 1980 are relics from the Neolithic Age with the highest altitude and most western longitude, which shows man lived and propagated on this land as early as 5,000 years ago and that a primitive village had been formed at that time. Local residents had begun planting millet and raising pigs. They also hunted foxes, black sheep and red deer as a supplement. Zhagyab County is where Gesar and Jomba waged a war for salt as depicted in "Jamba", a chapter from a Tibetan epic King Gesar. According to traditional Tibetan geographical concept, this is also Chawagang of the Six Mountain Ranges in DorKang, which is famous for salt production. Archeological surveys have discovered many stone walls and stone steps left over by "Jomba" people.
During the Tubo period (7th-9th century), Chamdo was the location of the famous Dongnu (Eastern Daughter) State and the Supi State. The Old Books of Tang recorded that the East Daughter State is another name of western Qiang. As there is another state of daughters in the western sea, this is called the Eastern Daughter State. They always had women as their Queens. Textual research of Ren Naiqiang, a famous Tibetologist, also shows the present Chamdo was once the political, economic and cultural center of the Eastern Daughter State. Cultural tracks of the two states can still be found today in this area.

In the 13th century, the Yuan emperors returned Tibet to Chinese territory and set up Dorgangsi Pacification Commissioner's Office in Chamdo and Garze of Sichuan Province. In the Ming (1368-1644) Dynasty, the Gelug Sect of Tibetan Buddhism sprang up, with its influence penetrating into the Kham area, forming the Hutogtu--big Buddha reincarnation system. The Ming Government set up the Dorgang Commander's Office here, entrusting the power to tribal chiefs and big lamas of monasteries. At the end of the Ming Dynasty, the Chamdo Prefecture was under the control of Gushri Khan, who was Hoshot Mongo's Baili Headman. In the Qing (1616-1911) Dynasty, emperors appointed some living Buddha and Tusi (hereditary headmen) to govern their own land, who were responsible for officials sent to Tibet by the Qing Government and the Dalai Lama. The Qing emperors also set up a grain station in Chamdo and sent civil and military officers there. They also dispatched 130 soldiers from Sichuan and Yunnan provinces to be stationed in Chamdo so as to pass on imperial edicts and protect the big living Buddha in the Chamdo Monastery and the grain station. At the end of the Qing Dynasty, Zhao Erfeng changed the name of Chamdo into Chuanbian (meaning the Sichuan border). After 1912 when the Republic of China was founded, it became a part of Xikham Province. In 1918, the local Tibetan government changed it to the Dormai Prefecture and set up "Dormai Jikyiu", which was divided into 25 sections.

On October 19, 1950, the People's Liberation Committee was set up in Chamdo Prefecture, which administered three areas: The Chamdo Liberation Committee had jurisdiction over 13 sections; the 39-nationality area governed 10 sections and the No.2 Office of the Bome area governed three sections and Yanjing and Zayu. All the 28 sections were under the direct control of the Government Administration Council. In 1955, the Tibet Autonomous Region Preparatory Committee was established, and the Chamdo Prefecture was included within its administration. At the beginning of 1960, the Commissioner Office of the Chamdo Prefecture was set up, which was located in Chamdo Town.