Wang then successively served in three regional roles: vice governor of Guangdong, Party secretary of Hainan, and Mayor of Beijing.

After graduating high school, Wang worked as a sent-down youth in the countryside, performing manual labour with peasants on a commune in the revolutionary heartland of Yan'an, where he met and befriended Xi Jinping.

At the height of the Asian Financial Crisis, Wang assisted then Guangdong Party Secretary Li Changchun in managing non-performing loans of various state-owned enterprises in the province.

Next, Wang served as the General Office chief of the State Economic Structural Reform Commission (国家经济体制改革委员会).

Wang took over from disgraced Beijing mayor Meng Xuenong when SARS struck the city in spring 2003, at which time he had only served as the Party Secretary in Hainan for five months.

In contrast to the lack of transparency during the administration of his predecessor, Wang called for a daily press release on the latest information about SARS.

In March 2005, during a local radio show, Wang apologized on air to the Beijing public for an ongoing natural gas supply shortage in the city.

But it was reported that during Wang Qishan's mayorship, he did not get along with Liu Qi, then Party Secretary of Beijing and a member of Politburo.

"[11] Wang's assuming the leading anti-corruption post was believed to be at least partly owing to his relationship with Xi Jinping.

[13][14] He also became the Leader of the Central Leading Group for Inspection Work, responsible for dispatching teams to the provinces and state-owned enterprises with the goal of rooting out corruption.

[19] In October 2024, he succeeded Zhu Rongji as the honorary chairman of the advisory board of the Tsinghua University School of Economics and Management.

U.S. Secretary of the Treasury Henry Paulson said that Wang is "decisive and inquisitive" and "an avid historian, enjoys philosophical debates and has a wicked sense of humor".

Wang managed the largest bankruptcy restructuring in China's history in 1998 and thereby prevented a banking crisis that could have crippled the country's growth.

"[10] Wang is a fan of the American television series House of Cards, and has frequently alluded to the show during anti-corruption conferences; he has said that he was especially fascinated by the role of the party whip.