Jang released her debut album First Story with the title track Burying My Face In Tears. Initially, it was not well received and only reached number 12 in Korean music charts. After starring in the popular sitcom New Nonstop, she became more well known and released the other tracks in the album such as her pop ballad style song, Confession and the April Story, ranked at the top in various music charts. The album sold 300,000 copies. Jang then became a host for MBC's music show, Music Camp and KBS's talk show Love Story. By the end of 2001, she received several New Female Artist awards from year-end Music Awards ceremonies and New MC awards from Entertainment Awards ceremonies.

In 2002, Jang landed her first leading role in a drama in SBS's romantic comedy Successful Story of a Bright Girl. The drama is well received and recorded high audience ratings. She won the Best New TV Actress Award at the 2003 Baeksang Arts Awards. The success of the drama and her hit song "Sweet Dream" launched her to stardom in South Korea that year. The same year, she starred in another romantic comedy series My Love Patzzi which also attained high ratings.

In 2003, she made her feature film debut in the film Oh! Happy Day.

In 2004, Jang was named public relations envoy for China by the Embassy in Korea of the People's Republic of China.

In 2005, with her increasing popularity in China, she made a bold move by moving to China to start her singing and acting career. Her first mainstream Chinese drama is Bratty Princess. The success of Bratty Princess catapulted her as a hallyu or Korean Wave star in China. She made several other drama series in China which includes Good Morning Shanghai in 2007, Iron Masked Singer in 2010, and Unruly Qiao in 2011.

In 2007, Jang held a fund-raising concert for child patients of leukemia in China. The Jang Foundation was established from the money raised during Jang's fan club meeting at her June 9 concert in Beijing, which was held to mark the 15th year of diplomatic relations between China and South Korea. Twelve hundred seats at the concert venue sold out early. After the concert on stage, a Chinese charity organization appointed Jang as a goodwill ambassador, making her the first foreigner to receive such an honor. The same year, she was appointed as one of the goodwill ambassadors for the China-ROK Exchange Year.

In the aftermath of the 2008 Sichuan earthquake, Jang donated 150,000 dollars to a charity organization in China and 8 billion won of clothing for the victims.

In 2009, she returned to the big screen with Sky and Ocean, playing a gifted Violinist with a mental age of 6 years old, diagnosed with Savant syndrome. The movie was a commercial failure, and was criticized for Jang's unfair nomination at the Grand Bell Awards even before the movie was released. However despite the controversy, Jang won the Best Actress for a Foreign Film Award at the 19th China Golden Rooster and Hundred Flowers Awards. The film also became the first Asian film to be invited to the 8th Tirana International Film Festival in Albania, where it won the Media Award.

In June 2010, Jang was appointed as an associate professor at the Beijing Huajia University.

In 2011, Jang was appointed as Seoul’s Gangnam-gu's ambassador to promote tourism in the area.

In December 2012, Jang reunited with her Baby Faced Beauty co-star Choi Daniel for KBS's teen drama School 2013. She received her second consecutive Excellence Award for an Actress in a mini-series at the 2012 KBS Drama Awards.

After filming for School 2013 concluded, Jang immediately returned to China to film a drama titled Red Palaquin.

The year 2014 proved to be a busy year for Jang with three TV projects under MBC network. In July 2014, Jang played the lead role in Fated to Love You, the Korean adaptation of the 2008 Taiwanese hit drama of the same title. This TV series reunited her with Jang Hyuk 12 years after both starred in the highly rated drama Successful Story of a Bright Girl. Fated to Love You was a hit in China and gained 200 million views. Shortly after, Jang starred in a one-episode drama special entitled Old Farewell for MBC's Drama Festival, pairing her once again with Jang Hyuk. She then took on the lead role opposite Shin Ha-kyun in the fantasy-romantic-comedy drama Mr. Back. She later won the 2014 MBC Drama Awards Top Excellence Award Best Actress in a Mini-Series for both TV drama series she starred in that year.

In 2015, Jang was recognized for her charity activities by the Ministry of Health and Welfare.

In 2017, Jang was cast in the drama Housewife Detective where she will play the role of a single mother. However due to production issues, filming of Housewife Detective was indefinitely suspended. Later in the year, she was cast in the romantic fantasy drama Confession Couple. The series was a success, and won acclaim from viewers.