His ancestors hailed from Jiangzhou 江州 in the commandery of Bajun 巴郡 (today in Chongqing), but He himself was born in Zhijiang 枝江 in Nanjun 南郡 (today in Hubei). In the late years of the Eastern Han period 東漢 (25-220 CE), Dong He and his family migrated to the province of Yizhou 益州 (Sichuan) that was controlled by Liu Zhang 劉璋 (d. 219). Dong held several posts in the local administration, and finally rose to the position of city magistrate (ling 令) of Chengdu 成都. He was known for his loyalty, austerity, and uprightness, and was able to establish good relationships with the native non-Chinese inhabitants of the region.
When Liu Bei occupied the province, Dong He declared his loyalty to the new master of the region and served as head of the bodyguard (zhonglangjiang 中郎將), a function in which he closely cooperated with Zhuge Liang 諸葛亮 (181-234) in military matters. Working in the office of the Commander-in-chief of the Left General (zuo jiangjun da sima fu 左將軍大司馬府事), Dong played an important role in the stabilization of Liu Bei's rule over Sichuan.