Dong hailed from Lintao 臨洮 (modern Minxian 岷縣, Gansu), a region at the border to the Tangut Qiang 羌 tribes. He spent his the early years of his career in this region as a military commander of the border garrisons. During the last years of the reign of Emperor Huan 漢桓帝 (r. 146-167) he was promoted to gentleman of the palace guard (yulinlang 羽林郎) and then, upon recommendation by the Leader of the court gentlemen (zhonglangjiang 中郎將) Zhang Huan 張奐, to court attendant (langzhong 郎中), and took over the post of commandant of the centre (wuji xiaowei 戊己校尉), regional inspector (cishi 刺史) of the province of Bingzhou 幷州, and was then appointed governor (taishou 太守) of the commandery of Hedong 河東 in the centre of the empire.
After the outbreak of the Yellow Turban uprising 黃巾起義 and during the rebellion of Bian Zhang 邊章 and Han Sui 韓遂, he successfully put down the rebellions and pacified the northeastern part of China. For these merits, he was appointed Chamberlain for the Palace Revenues (shaofu 少府) in 189, but he declined. Instead, Emperor Ling 漢靈帝 (r. 167-188), facing death, appointed him regional governor (mu 牧) of Bingzhou, a position in which he was able to built up a powerful army.
After Emperor Ling's death in 189, general-in-chief (da jiangjun 大將軍) He Jin 何進 and metropolitan commandant (sili xiaowei 司隷校尉) Yuan Shao planned to extinguish the powerful eunuch clique at the court and invited Dong Zhuo to participate. The plot was discovered by the eunuchs, and He Jin was executed.
Yuan Shao could not but take action, assailed the imperial palace and massacred all eunuchs. Zhang Rang 張讓 and Duan Gui 段珪 seized the Infant Emperor (Shaodi 少帝, r. 188-189) Liu Bian 劉辯 and the Prince of Chenliu 陳留, Liu Xie 劉協, and escaped from the capital. At this point of time Dong Zhuo marched his troops towards the capital, sent out Lü Bu 呂布 to assassinate Ding Yuan 丁原, the Chamberlain for the Imperial Insignia (zhijinwu 執金吾), and seized the two imperial children.
Dong Zhuo installed the Prince of Chenliu, Liu Xie, as the new emperor (known as Emperor Xian 漢獻帝, r. 189-220). Dong was made Defender-in-chief (taiwei 太尉) and Counsellor-in-chief (xiang 相) and was given the title of Marquis of Mei 郿侯. As the most powerful person of the empire, Dong Zhuo abused his position, embezzled funds and built up his own factual empire.
The continuing rebellions of adherents of the Yellow Turbans roamed the eastern part of the empire without that any army was able to suppress them. To these disturbances came a lot of officials rebelling against Dong Zhuo's abuse of power, like Sun Fu 孫馥, Yuan Shao and Sun Jian 孫堅. Dong Zhuo therefore burnt down the capital Luoyang 洛陽 and transferred the court back to the ancient capital Chang'an 長安 (modern Xi'an, Shaanxi). In 191 he had made himself Grand Preceptor (taishi 太師), which was the highest position of state officials and allowed him to wear the same robes as the emperor and to drive in imperial chariots.
Dong Zhuo also managed to have all his male relatives given titles of nobility. Lü Bu, Dong Zhuo's foster-son, the Minister of education (situ 司徒) Wang Yun 王允 and the Vice Director of the Secretariat (puye 僕射, sic!) Sun Rui 孫瑞 thereupon conspired and decided to assassinate Dong Zhuo, which happened during a court session in 192. His death was frantically celebrated throughout the empire.