His father, 'Dus-srong, died in 704 in battle in Mywa (probably = the Miao people) territory in 'Jang (Nanzhao) in modern Yunnan. The Tang Annals state he was on his way to suppress tributary kingdoms on the southern borders of Tibet, including Nepal and parts of India. There was a dispute among his sons but, "after a long time" the people put Qilisuzan (Khri-lde-gtsug-btsan) or Mes-ag-tshoms, aged only seven, on the throne.
Beckwith states that in the winter of 704-705, Lha ("Balpho" or Lha Balpo), one of the sons of 'Dus-rong, took the throne, but Khri ma lod, the dowager empress, wife of Mangsong Mangtsen and mother of 'Dus-rong Mang-po-rje, "dethroned Lha in favor of the infant Rgyal Gtsug ru, the future Khri gtsug brtsan, popularly known as Mes ag tshoms. Revolts and executions accompanied the virtual coup, but the Annals and Chinese sources have little to report on them. It is interesting to note that Lha apparently was not killed, but only forced into semiretirement. It was thus, perhaps, the "Retired Emperor" Lha who actually received and married the Chinese princess Chin-ch'eng in 710. In any event, Tibet experienced more internal unrest, and was conspicuously quiet on its borders with China.
Whatever the case, Mes-ag-tshoms was crowned king in 705 CE, although he was not formally enthroned until the death of Khri ma lod in 712.
The Chinese princess Jincheng Gongzhu (?-739), Zongli, the "real daughter" of the king of Yong, and an adoptive daughter of Emperor Zhongzong of Tang (r. 705-710), was sent to Tibet in 710 where, according to most sources, she married Mes-ag-tshoms, who would have been only six or seven years old at the time. She was known in Tibet as Gyim shang Ong co, or, simply, Kim-sheng or Kong-co, and was a devout Buddhist.
Five Buddhist temples were built at: 'Ching bu nam ra, Kwa chu in Brag dmar, 'Gran bzang, 'Khar brag and sMas gong.
Buddhist monks from Khotan (Li), fleeing the persecutions of an anti-Buddhist king, were given refuge by Kim-sheng about 737. The story of these Khotanese monks is recorded the Li yul lung-btsan-pa or 'Prophecy of the Li Country', a Buddhist history of Khotan which has been preserved as part of the Tibetan Tanjur.
Kim-sheng died during an outbreak of smallpox sometime between 739 and 741. The rise of anti-Buddhist factions in Tibet following the death of the Chinese princess began to blame the epidemic on the support of Buddhism by the king and queen. This forced the monks to flee once again; first to Gandhara, and then to Kosambi in central India where the monks, apparently ended up quarreling and slaughtering each other.
Mes-ag-tshoms had two other wives, a noblewoman from the Nanam clan, Mang-mo-rje bZhi-steng, who died in 730, and a princess from 'Jang (Nanzhao) called lCam lHa-spangs.
In 717 the Tibetans (according to an 11th century Chinese history) joined with the Turkic Türgish to attack Kashgar.
In 720 Tibetan troops took the Uighur principality of 'Bug-cor in the Dunhuang oasis.
In 727 the king left to take control of the government of the 'Azha in hand. He then seized the important Chinese fortress of Kva-cu or Guazhou at (Anxi), to the southeast of Dunhuang, which contained supplies for all the Chinese-dominated territories as far as the Western Turks (Dru-gu) to the north and the Tazig (Arabs) to the west, and all this wealth fell into the hands of the Tibetans so that even ordinary Tibetans had fine Chinese silks to dress up in. However, the Chinese managed to drive the Tibetans away in 728, after a siege of eighty-days.
In 724, according to a Chinese encyclopedia of 1013, the Chinese princess, Kim-sheng secretly wrote to the ruler of Kashmir asking for asylum, but apparently nothing came of this.
In 730 a peace treaty with China was signed which established the border east of Kokonor at the Chiling Pass in the Red Hills. In 733 Mes-ag-tshoms wrote to the Chinese emperor Xuanzong (r. 712-756) stating that China and Tibet were equally great kingdoms and hoping that peace would endure. In 734 a pillar engraved with the treaty was erected, and although it was apparently torn down soon after, envoys travelled regularly between the Lhasa and Chang'an for the next fifteen years.
In 736 Tibet again attacked Bru-sha (Gilgit), and the ruler came to Tibet to pay homage. later that year the Chinese also attacked Bru-sha, but in 740 the Tibetan princess Khri-ma-lod married the ruler of Bru-sha.
In 738 the 'Nine Loops of the Huang Ho', which had been given to Tibet as part of a dowry, were retaken by the Chinese.
In 740, the Chinese also regained control of the key fortress at Anrong, just north of Chengdu, which the Tibetans had held for over sixty years. In 742 the Chinese also managed to recapture the formidable fortress of Shipu, near the border in the Red Hills.
In 747 the Chinese, under command of the Korean general, Gao Xianzhi, fought the Tibetans and forced them to leave the region.
Between 748 and 752, the king of the White Mywa, who formed part of 'Jang (Nanzhao) rebelled against Chinese rule and submitted to the king of Tibet.
Also in 751, Kag-la-bon (r. 748-779), the ruler of 'Jang (Nanzhao) in Yunnan, came to pay his respects to Mes-ag-tshoms. In 753 Mes-ag-tshoms sent him a golden diplomatic seal and in 754 and 756, Tibetan armies were sent to help the Nanzhao fight off the Chinese.