He hailed from Pingyuan 平原 (modern Huimin 惠民, Shandong). When Emperor Wu 漢武帝 (r. 141-87 BCE) mounted the throne, he was looking for magicians or Daoist masters (fangshi 方士) throughout the empire. Dongfang Shuo submitted a memorial introducing himself, and so he was appointed gentleman-attendant (lang 郎) and was later promoted to gentleman attendant-in-ordinary (changshilang 常侍郎) and was granted the honorific title of Superior Grand Master of the Palace (taizhong dafu 太中大夫).
Dongfang Shuo was known for his harmonious character, excellent words and splendid knowledge. He therefore often served Emperor Wu for courtial entertainment. Yet Dongfang also dared to directly address the emperor and pointing at his faults, especially his love for a prodigious style of luxury. Such a life would deprive the people of their livelihood and damage the revenues of the state. Emperor Wu did not love such criticism and continued his way of holding court.
Disappointedly Dongfang Shuo wrote the essays Dakenan 答客難 "Difficulties at answering a guest" and Feiyou xiansheng lun 非有先生論 "The treatise of Master There Is Nothing" in order to express his discontent. The first piece is written in a question-and-answer style and points at the situation that Emperor Wu did not esteem men of wisdom and capabilities. Its style has later been imitated by Yang Xiong 揚雄 (Jiechao 解嘲), Ban Gu 班固 (Dabinxi 答賓戲) and Zhang Heng 張衡 (Yingjian 應間). The second piece reports the story of a ficticious official in the ancient state of Wu 吳 (modern Zhejiang) who ceased to speak for three years. Asked by the king for the reason, he answered with a lot of examples from history in which the state was ruined by and improper conduct of government. Master There is Nothing was so able to awake the king and convince him of adopting the suggestions of his capable ministers.
Dongfang Shuo also wrote an elegiac rhapsody called Qijian 七諫 "Seven remonstrances". His collected writings originally were 2-juan long. The surviving fragments were been collected by the Ming-period 明 (1368-1644) scholar Zhang Pu 張溥 (1602-1641) to the book Dongfang Taizhong ji 東方太中集 that is included in the collection Han-Wei-Liuchao sanbai jia ji 漢魏六朝百三家集.
The Daoist biographical collections Shenyijing 神異經 and Shizhouji 十洲記 are attributed to Dongfang Shuo. They were in fact compiled by later Daoists that tried to enhance the credibility of their books by using the name of the revered master.