With ancestry in Guangshan County (光山縣), Henan, she was born Deng Wenshu (邓文淑) in Nanning (南寧), Guangxi. Growing up in the poverty-stricken family, her father died when she was at a young age and her single mother taught and practiced medicine. Deng participated as a team leader in the May Fourth Movement, where she met Zhou Enlai and married him in 1925 in Tianjin.
Deng and Zhou had no children of their own. However, she adopted several orphans of "revolutionary martyrs", including Li Peng, later a Premier of the People's Republic of China. She was instrumental in the abolishment of foot binding imposed on women.
She died in Beijing of illness at the age of 88.
There is a memorial hall dedicated to her and her husband in Tianjin (天津周恩来邓颖超纪念馆).