Following the success of Moment in Peking, Zhao starred in The Postmodern Life of My Aunt, which premiered at film festivals around the world, including the Toronto International Film Festival. Though Zhao only appeared ten minutes in the film, her performance led her to be nominated at the 43rd Golden Horse Awards and the 27th Hong Kong Film Awards for Best Supporting Actress.

In 1993, while Zhao was still in school, the movie A Soul Haunted by Painting (1994), directed by Huang Shuqin, starring Gong Li and Derek Yee, was filming in Wuhu. Zhao was cast for a cameo role, a young prostitute in the brothel where Gong's character works. This is her first acting experience. She appeared briefly at the beginning of the film and had no dialogue.

Zhao had developed strong interests in acting after her first acting experience, and decided to become an Actress. In 1994, after graduating from the Wuhu Normal School, she gave up her job as an apprentice pre-school Teacher. She moved from her hometown to Shanghai and was enrolled in Xie Jin Star Academy, an acting school founded by the legendary Chinese Director Xie Jin, where she received structured acting training during 1994 - 1995. She was also selected by Xie to star his movie Penitentiary Angel (1996). This was her first substantial role. Though she did not find her own performance fulfilling, Zhao considered it a valuable experience and a good start of her career. The film landed her other roles in TV series including her first leading role in Sisters in Beijing (1996). "I was too young to understand the role," she said, "but if you've been cast in a film by a famous Director, no matter how well you did, other less-famous Directors will also want to cast you."

In 1996, Zhao was admitted to the School of Performing Arts, Beijing Film Academy (BFA) with the highest score national-wide. She graduated 4 years later with Bachelor Degree of Performing Arts from BFA as one of the most outstanding graduates - Zhao scored five "A"s and nine "A-"s out of the 14 courses. Her graduation thesis scored 90 (out of 100).

In 1997, renowned Novelist and Producer Chiung Yao was casting for the TV series My Fair Princess, a joint production by mainland China and Taiwan which was adapted from Chiung Yao's own novel. She identified Zhao Wei as a talent after watching Sisters in Beijing and offered Zhao the title role of Huan Zhu Ge Ge (Princess Pearl) a.k.a. Xiao Yanzi ("Little Swallow"), a rebellious and funny Princess who dared to challenge authority and rules in the Palace. Filming the series was an arduous task for Zhao and her co-stars; Zhao herself acknowledged the intensity of filming:

While studying at the Beijing Film Academy, Zhao rose to national and regional prominence overnight for her role as Xiao Yanzi ("Little Swallow") in the hit TV series My Fair Princess (1998–1999), for which she also won Golden Eagle Award for Best Actress. My Fair Princess enjoyed unprecedented success in East and Southeast countries, and Zhao is regarded by many as Mainland China's first "national idol" since the economic reform began in 1978.

The hard work of the cast yielded unexpected results. This comedic period drama quickly became a phenomenal sensation and swept TV ratings in Taiwan, mainland China, Hong Kong and Southeast Asian countries such as Singapore and Vietnam. Zhao rose to prominence and became a household name overnight. In 1999, she became the youngest Actress to win the Golden Eagle Award for Best Actress. She was regarded by many as mainland China's first "national idol", and was named one of Taiwan's "Top Ten Most Outstanding Individuals in Television Industry". She is also regarded as one of China's Four Dan Actresses. However, alongside the phenomenal success were increasingly negative critics in mainland China, attacking the rebellious role as a "bad influence" over children and youngsters. During Chinese People's Political Consultative Conference 2002, a member of the CPPCC submit a proposal to calling to boycott the "little swallow". Zhao once again worked with Chiung Yao for the 2001 television series Romance in the Rain, a costume drama based in the 1930s and 1940s. Opposite to the funny Princess she played in My Fair Princess, Zhao played a vengeful girl who tried to exact revenge against her parents. The series was a commercial success, and recorded the highest ratings of the year.

Alongside her acting career, Zhao has become actively involved in commercial work. In 2001, she was selected as one of "China's Top Ten Most Popular Commercial Models", the culmination of her work for Red Earth and Amoisonic Mobile Phone. The same year, Zhao was ranked second on "China's Top 10 Artists for Advertisements" list. South Korean television network KBS ranked Zhao number one in China and Japan and number two in South Korea, crowning her "Commercial Queen in 3 countries."

In 2003, Zhao starred in four films: My Dream Girl, Warriors of Heaven and Earth, Green Tea, and Jade Goddess of Mercy. After much speculation over who was cast for the female lead An Xin in Ann Hui's film Jade Goddess of Mercy, the role was finally offered to Zhao, and her performance was well received by critics. In 2004, the Chinese Association of Film Performing Arts presented her the Golden Phoenix Award for this role. She was also nominated at the 27th Hundred Flowers Award for Best Actress for her performance in Warriors of Heaven and Earth.

On several occasions, Zhao has been praised by the media for her sense of style. At the Lycra Channel Young Awards (now known as the China Fashion Awards), Zhao was chosen as the "Most Stylish Actress" in mainland China. The same year, MTV China also selected Zhao as the "Most Stylish Asian Actress". Zhao also garnered another fashion award at the 2004 Pierre Cardin Awards. Zhao was awarded the "Most Stylish Female Artist" and "Most Stylish Actor" at the China Fashion Award (CFA) in 2005. In 2007, Zhao won her the third "Most Stylish Actor" in China Fashion Awards. The same year, she won "Most Stylish Female Artist" at the MTV China Style Gala.

After a four-year break from television series, Zhao starred as Yao Mulan in a remake of Lin Yutang's Moment in Peking (2005). The television series became Zhao's fourth TV drama (after My Fair Princess, My Fair Princess 2 and Romance in the Rain) to become the highest rated drama of the year. Zhao was nominated at the 26th Flying Apsaras Awards for Outstanding Actress.

In 2006, Zhao made a surprising move by sitting for the national entrance exam for postgraduate studies. After passing with flying colours, Zhao returned to her alma mater, the Beijing Film Academy (BFA) in September 2006 as a postgraduate student in the Department of Film Directing, where she studied under Director Tian Zhuangzhuang. That year, Zhao was ranked No.4 on Forbes' 2006 China Celebrity 100 list. She was also selected as the "Most Beautiful Woman" in China through a national voting by Sina.com & Sohu.com's users. People magazine also listed Zhao as "100 Most Beautiful People" in 2006.

Zhao then portrayed a cabby in the 2007 film The Longest Night in Shanghai, starring alongside Masahiro Motoki and Dylan Kuo. The same year, Zhao starred in the television series Thank You for Having Loved Me. She reportedly received a salary of 100,000 yuan per episode.

After two known relationships, Zhao Wei married Chinese businessman Huang Youlong in 2008 in Singapore. The couple's daughter, was born in April 2010.

On 6 August 2009, she was elected vice-president of China Film Performance Art Academy and executive member of the council of the China Environmental Society.

In June 2010, she returned to limelight as a jury member of the 13th Shanghai International Film Festival.

As of 18 April 2011, Zhao is climbing up the ranks of the most followed microbloggers worldwide. Her fan count has exceeded six million, bringing her ever-closer to American celebrities Ellen DeGeneres, Ashton Kutcher and Katy Perry, all of whom also recently surpassed the six million fan mark.

In 2012, she graduated from the directing institute of Beijing Film Academy, with an MFA dissertation defense score of 99/100, ranking #1 out of all the graduates.

From 2013 to 2014, Zhao as the spokeswoman of Samsung Galaxy Note 3. Since 2012, Zhao selected as the official amabassador of Jaeger-LeCoultre.

Wei and her husband purchased stakes in Ali Baba Pictures in 2014, leading to tens of millions of dollars in gains over the next two years. Near the end of 2016, her company Longwei Culture & Media purchased control of Zhejiang People Culture, a Chinese animation studio and mobile Gaming company listed on the Shenzhen Stock Exchange, for CN¥3 billion. Although the acquiring company have answered the Shanghai Stock Exchange questions, several mainland China media and some netizens still boycott it, regard the buyout by a female actor as "the hen cackles in the morning". Furthermore, nationalists combined with ultra-left media attack Zhao continuously. Finally, original banks quit for "uncertainty", causing the acquisition to fail.

In 2015, she starred in comedies Hollywood Adventures and Lost in Hong Kong, both of which were commercially successful. Forbes described Zhao as the "world's wealthiest working actress". The same year, Zhao made her return to television in Tiger Mom. She was nominated at the Asian Television Award and Magnolia Award for Best Actress. On 20 October, Zhao elected as executive member of Executive Committee of China Film Directors' Guild.

Zhao completed her second directorial feature No Other Love in June 2016. On 1 July 2016, the Communist Youth League used its own website and social media to criticize Zhao over the male cast and Taiwanese director-actor Leon Dai's alleged support for Taiwanese independence. It posting on Weibo called for boycott of this movie. Following the call, China's nationalists and nationalist unions started to attack Zhao for being a "public enemy" and "traitor" to the nation. The nationalists also branded Zhao as an "American spy", citing Zhao had taken a photo and shaken hands with Hillary Clinton at the Global Alliance for Clean Cookstoves Future Summit in Manhattan, US on 20 November 2014. In early July, both Dai and Zhao and their movie production studios issued apology statements but the nationalists continued to attack them, even against Zhao's family members including her husband, daughter and brother. On 15 July 2016, under fierce online assault, Zhao apologized, and the movie studio also announced its plan to replace Dai. The incident generated much debate online, and some famous Chinese Writers, professors and filmmakers, including Fang Fang, Sai Ren, Shi Hang, Yan Feng, He Ping, Chen Guoxing, along with People's Daily's social media and China Newsweek (present by China News Service) categorically denounced the online abuse and/or voiced their support for Zhao.

In February 2017, Zhao went back to her alma mater - School of Performing Arts, Beijing Film Academy - to be the finale round examiner/assessor of applicants for the 2017 intake. The entrance exam is said to be the most challenging one of students pursuing performing arts whereby the success ratio is 1:113. In September, she was named as a member of the main competition jury for the 30th Tokyo International Film Festival.

In March 2018, Zhao Wei was named as a member of the finale-round jury for the 9th China Film Directors Guild Award.