In November 1965, at the beginning of the Cultural Revolution, he came under attack for a play he wrote about an upright Ming dynasty official called Hai Rui Dismissed from Office, which was widely understood as an anti-Mao allegory.

With support from the Wu clan organization and with the money from selling his mother's jewelry, he attended university preparatory schools in Hangzhou and then in Shanghai, where he was inspired by the lectures of Hu Shih.

Wu stayed at Tsinghua as a teaching assistant but began to publish important articles on Ming dynasty history using critical techniques to resolve old controversies and raise new questions.

Wu subsequently turned the essay, after multiple revisions, into the Beijing opera Hai Rui Dismissed from Office, which was performed in 1961 to great acclaim.

Subsequently, "...the hypervigilant Jiang Qing and Kang Sheng decided [it] was ... 'related to the Lushan Conference and ... implicitly endorsed 'assigning output quotas to households' and the ongoing verdict-reversal wind.

"[5] The subsequent attacks on the play and Wu Han were actually aimed at the mayor of Beijing, Peng Zhen, a pillar of the Chinese Communist Party ("CCP") establishment that Mao wanted to take down.

The leftist literary critic Yao Wenyuan, later appointed to the Politburo of the Central Committee of the Chinese Communist Party and who became known as one of the Gang of Four, fired one of the opening shots in this struggle on November 10, 1965 when he published an article in Wenhui Bao attacking Wu and his play on the grounds that Hai Rui was metaphorically equated with Marshal Peng Dehuai, who had criticized Mao for launching the Great Leap Forward and who had been purged as a result.

Yao Wenyuan argued that therefore Wu Han had equated Mao himself with the un-approachable Ming emperor who dismissed the righteous Hai Rui from office.