Nie joined the Communist Party of China in 1938 as a middle school student.
Nie's big-character poster was put up on 25 May 1966. In it, she criticised Song Shuo, deputy director of the Beijing Municipal University Bureau, Lu Ping, the President of Peking University and head of its Communist Party committee, and Peng Peiyun, an official in the Beijing Municipal University Bureau. Although Nie's main criticism was the control of Peking University by the bourgeoisie, the aim of the campaign was to legitimise the purge of the Beijing municipal party chief Peng Zhen, by exposing his crime of supporting a bourgeoise reactionary education line. This was pushed by members of the radical clique surround Mao Zedong, including Kang Sheng and Cao Yi'ou. This inspired students at other universities to write posters, most of which expressed support for the 'revolutionary action' of Nie Yuanzi.
When she published the poster, Nie was one of Peking University's top 30 officials on the Party committee. She was married to an official in the Central Commission for Discipline Inspection and, along with her husband, Nie often socialised with ministerial-level officials.
Nie initially supported the persecution of other academics, but later disagreed on the course the Cultural Revolution was taking and tried to quit her position in the Red Guards. She controlled revolutionary activities at Peking University, along with her colleagues, protected by her status as a celebrated rebel.
Nie was made an alternate member of the 9th Central Committee of the Communist Party of China. In December 1969, she was sent to labour at a farm owned by Peking University in Liyuzhou (Chinese: 鲤鱼洲), Jiangxi. She returned to Beijing in 1970 to recuperate from illness.
In 1971, Nie was subjected to examination and her movements were restricted. In 1973, she was sent to work in the Xinhua Printing House, where she lived, ate and slept in the factory. She moved to a factory that made apparatuses for Peking University in 1975. On 19 April 1978, Nie was sent to Yanqing Prison.
Nie is critical of the post-Mao Chinese regime and has expressed a desire for greater freedom of opinion.
In 2005, Nie's memoirs were published.
In Ji Xianlin's memoir Cowshed: Memories of the Chinese Cultural Revolution, Xianlin speaks of her capriciousness, cruelty and remarkable arrogance.