In 1990, at the age of four, Yang made her acting debut in the historical television series Tang Ming Huang directed by Chen Jialin, playing the role of young Princess Xianning. She also had a minor role as Beggar So's daughter in King of Beggars (1992), which starred Stephen Chow as the titular character. Two years later, she starred in the television series Hou Wa, where her acting left a deep impression on the Producer.
In the late 2000s, Yang started to gain media attention with her roles in The Return of the Condor Heroes (2006) and Wang Zhao Jun (2007). Her popularity further rose after starring in the popular fantasy drama Chinese Paladin 3 (2009) as the female lead.
In 2002, Yang received her first script and made her official acting debut in The Story of a Noble Family.
She then starred in Li Shaohong's The Dream of Red Mansions (2010). Although her role was minor, she received praise for her acting. The same year, she starred in big-budget historical series Beauty's Rival in Palace, winning acclaim for her role as a cold Assassin.
Yang achieved widespread fame with the time-travel hit, Palace (2011). She was voted the Most Popular Actress at the 17th Shanghai Television Festival. The theme song of the drama sung by Yang, titled "In support of the love", also topped China music portals and won Best Theme Song (OST) at the 6th Huading Awards. The same year she starred in horror film Mysterious Island, which raked in more than 70 million yuan at the box office and became the most successful horror film in China.
Yang then starred in Beijing Love Story (2012), a modern romance drama directed by Chen Sicheng. The series was a hit, and Yang was once again voted the Most Popular Actress at the 9th China Golden Eagle TV Arts Festival. The same year she co-starred in Painted Skin: The Resurrection, a sequel to Gordon Chan's 2008 box office hit Painted Skin.
In early 2012, Yang Mi revealed her relationship with an Hong Kong actor-singer Hawick Lau through her Weibo. Then on November 11, 2013 she announced their engagement. Yang Mi and Hawick Lau were married in Bali, Indonesia on January 8, 2014. Their wedding was attended by Tiffany Tang, Yang's close friend in the entertainment industry and her co-star in Chinese Paladin 3 (2009).
On June 1, 2014, she gave birth to their daughter by cesarean section, Noemie Lau nicknamed Little Sticky Rice (小糯米) at the Hong Kong Adventist Hospital, Hong Kong.
In 2015, Yang starred in romance films You Are My Sunshine with Huang Xiaoming and Fall in Love Like a Star with Li Yifeng. She also challenged the role of a blind girl in The Witness, a remake of the South Korean thriller Blind.
Yang made her small-screen comeback in the television drama The Interpreter, which premiered on Hunan TV. The series was a ratings success, and became the highest-rated drama of 2016. She also featured in L.O.R.D: Legend of Ravaging Dynasties, directed by Tiny Times Director Guo Jingming. The same year, Yang became a cast member of Hunan TV's reality show, Takes a Real Man 2.
In 2017, Yang starred in Eternal Love, adapted from the xianxia novel Three Lives Three Worlds, Ten Miles of Peach Blossoms by TangQi GongZi. The fantasy-romance drama was a massive hit both locally and internationally, and Yang received acclaim for her acting performance in the drama. She then starred in Reset produced by Jackie Chan, which led to her win for Best Actress at the 50th WorldFest-Houston International Film Festival. Yang next starred in wuxia film Brotherhood of Blades 2 alongside Chang Chen. She ranked third on Forbes China Celebrity 100 list, her highest ranking yet.
In 2018, Yang starred in The Negotiator, a modern drama which deals with the profession of negotiators.