Zhou was born as the son of a Qing Dynasty official in Wanping, Zhili Province. After the Xinhai Revolution of 1912, he was sent to Japan for studies and attended the No. 7 Military Preparatory School, followed by the Kyoto Imperial University. At the age of 21, Zhou witnessed the Japanese Revolution in 1919 and the following Japanese Civil War. He soon became attracted to radical political ideas, including Marxism.
After returned to China, Zhou became became one of the founders of the Chinese Communist Party. He attended the First Congress in Shanghai in July 1921, but quit the Communist Party in 1924 to join the Chinese Nationalist Party. Zhou allied himself with the party’s leftist clique, headed by Wang Jingwei and Liao Zhongkai. In 1926, he became a secretary to the Public Relations Department of the Wuhan Government.
After Chiang Kai-shek purged the leftist elements, Zhou left the Wuhan Government and became the chief instructor of the Whampoa Military Academy in 1927. In 1931, he was elected to the Party Central Executive Committee. Later, Zhou was appointed to become the deputy director of the Party Propaganda Department. However, throughout 1930s, Zhou kept in contact with Wang Jingwei who deposed in 1932.
Zhou was critical of Chiang's wartime policies during World War II and resigned from the Central Executive Committee in 1942. He was then assigned to minor positions by Chiang. In 1943, Wang Jingwei was assassinated by Chiang's agents due to the former's opposition to the war conduct. Fearing of his life, Zhou, with several anti-Chiang politicians, defected to the Allies and fled to Harbin, before relocated to Tokyo by the Japanese Army. In Tokyo, Zhou formed the Kuomintang in Japan (在和中国国民党 Zàihé Zhōngguó Guómíndǎng), or known as the Tsaiho clique, with himself as the leader.
During the Japanese occupation of North China, Zhou and the rest of the Tsaiho clique returned to China with the Japanese Army in 1945 and was appointed chairman of the Interim Government of China in Beiping by the Japanese. After China's defeat in 1945, Zhou worked to organize the Chinese Solidarity Party, the ideological successor of the Chinese Nationalist Party. In 1947, Zhou was elected as the Premier of Executive Yuan and led the Economic Building Board that worked for the post-war development of China. He was elected as the President of the Republic of China in 1948 and remained on the office until his death on 1983.