Wang signed his first professional contract with Chinese Basketball Association side Bayi Rockets in 1994. When the Chinese Basketball Association first started in 1995, Wang was one of the youngest players to play in the league. Nevertheless, he soon became a starter in the star-studded team. From 1995 to his departure for the National Basketball Association in 2001, Wang and the import-less Bayi Rockets won all of the CBA championships, however, Bayi's dynasty was upended by Yao Ming and the Shanghai Sharks as soon as Wang left for the National Basketball Association. After the 2004–05 season, Wang returned to China and rejoined the Bayi Rockets in the Chinese Basketball Association. In March 2007, he guided Bayi to win the CBA championship for the seventh time in the team's history over the Guangdong Southern Tigers and was named the most valuable player of the series. Wang announced his retirement at the end of the 2013–14 season.
To the surprise of almost all Chinese basketball officials and reporters, the Dallas Mavericks of the National Basketball Association selected Wang with the 36th pick in the second round of the 1999 NBA Draft. Dallas were the only team that got hold of Wang's official documents with an authentic date of birth, thanks to his agent Xia Song who was in Dallas on draft night. Unprepared and confused, the Bayi Rockets refused to allow their only center leave for the National Basketball Association, at least immediately.
After long periods of negotiations, Wang was finally let go by his team and the Chinese basketball officials to pursue his NBA dream, two years after he was drafted. He became the first ever Chinese player to play in the National Basketball Association. Wang arrived in Dallas after winning his last CBA championship title when there were less than ten games left in the 2000–01 season. Despite some adjustment difficulties, Wang managed well by averaging 4.8 points per game and 1.4 rebounds per game, making the team's playoff roster. Two days after Dallas were eliminated from the playoffs, Wang hurried back to China to play in the 2001 East Asian Games according to an agreement formed between the Chinese authorities and the Dallas Mavericks. However, Wang still had one obligation to fulfill before being allowed to return to the National Basketball Association. His former club Bayi requested that he stay in China to play in the 2001 National Games in November 2001. Wang returned to Dallas after barely defeating Yao Ming's Shanghai team by one point in the final, but he found that he had a lot of catchup to do as other players already had two months of preparation and training.
Wang's contract with Dallas expired after the 2001–02 season. With his future up in the air, he decided that he would spend the summer in the United States, rather than returning to China for training, as the Dallas Mavericks had promised the Chinese basketball officials. Wang fired his agent Xia Song when the latter suggested otherwise, and following the advice of his American-born Chinese friend Simon Chan, moved to Los Angeles without telling either Dallas or his Chinese side about his intentions. During his stay, Chinese basketball officials faxed two letters to him urging him to return to China as soon as possible to train with the Chinese national basketball team. A major blow to all parties involved was an article by Jodie Valade that appeared in The Dallas Morning News which hinted that Wang, who had not yet stated his intentions, might consider defecting to the United States. China sent two military officials who had known Wang very well to go to the United States for a final negotiation. During a press conference, Wang stressed that the relationship between him and the Chinese was like one between "a son and a mother", and the conflict was all but misunderstanding. He was ultimately dismissed from the Chinese national team for failing to return to China for practice in 2002.
Wang signed for the Los Angeles Clippers in 2002 and after a season with them, he was placed on waivers. The Miami Heat decided to sign Wang to a multi-year contract after picking him up. He became a free agent at the end of the 2005 season after playing for two seasons with Miami.
On 10 April 2006, following weeks of rumors from the Chinese media, Wang returned to China from the National Basketball Association after being expelled from the national team for four years due to conflicts with Chinese officials. He publicly apologized for his past mistakes and stated that he wanted to represent his national team in the 2006 FIBA World Championship as well as the 2008 Summer Olympics. Over a period of four weeks in the lead-up to the 2006 FIBA World Championship, Wang Zhizhi was a significant contributor to the Chinese national team in the absence of injured Houston Rockets player Yao Ming, scoring 4.3 points per game and 2.6 rebounds per game in eight matches before suffering a torn ligament during a friendly against France in July 2006. Wang recovered in time to play in the tournament and averaged 8.2 points per game and 3.5 rebounds per game.