She has collaborated with master director Hou Hsiao-hsien on three films: Millennium Mambo (2001), Three Times (2005), and The Assassin (2015).

Shu Qi has also played leading roles in both art-house films and box-office hits, including If You Are the One (2008) by Feng Xiaogang, Journey to the West: Conquering the Demons (2013) by Stephen Chow, Gone with the Bullets (2014) by Jiang Wen, and Mojin: The Lost Legend (2015) by Wuershan.

[10] She has since appeared in Hong Kong films such as Portland Street Blues (1998), City of Glass (1998), the box office hit Gorgeous (1999), Stanley Kwan's The Island Tales (1999) and Hou Hsiao-hsien's Millennium Mambo (2001), making her transition into mainstream acting.

Among Shu's earlier notable works were The Foliage (2004), a romance film set in Yunnan during the Cultural Revolution.

[16] She also starred alongside Tony Leung Chiu-wai and Takeshi Kaneshiro in the crime drama Confession of Pain.

[19] The same year, she was honored at the Huabiao Awards as Best Actress for the Taiwan and Hong Kong region for her performance in the romantic comedy film If You Are the One, directed by Feng Xiaogang.

[25] The same year, she starred in the blockbuster film Mojin: The Lost Legend, adapted from popular adventure novel series Ghost Blows Out the Light.

[26] In 2016, Shu, Feng Shaofeng and Victoria Song starred in the Chinese remake of My Best Friend's Wedding.

In 2009, she, along with Frederique Constant and Paint-a-Smile Foundation, repainted the murals on the walls of the cardiology department at the Beijing Children's Hospital.

[44] In January 2025, American luxury beauty brand Estée Lauder named Shu as its global spokesperson for skincare.