Chen was born in Wuxi, Jiangsu. He studied at Pomona College, where he graduated Phi Beta Kappa in 1920, and he then pursued a M.A. in history at The University of Chicago. In Spring 1922, he enrolled at Harvard University for a history PhD; there he assisted Charles Haskins. However, A year later, he left the United States for Germany, and completed his doctorate at Berlin University. In 1924, he earned an academic position at Peking University.
He was recruited to the Comintern, also in 1924, by Li Dazhao, as mentioned in his 1988 autobiography My Life During Four Eras. During the 1930s he came down on the Communist side of Mao Zedong, drawing on his field research on the economic conditions of Chinese peasantry for the Institute for Social Science Research. He wrote Landlord and Peasant in China (1936) on this area. He was one of Mao's theorists, and he spent time out of China in Moscow.
From 1945 to 1950, he resided in the USA. He then returned to China, an uncomfortable experience since he was accused of spying for the Kuomintang. Later in the Cultural Revolution, he was harshly treated.