Ferguson was a member of the female trio Wild Orchid, which she fronted with Stefanie Ridel and fellow Kids Incorporated star Renee Sandstrom. Wild Orchid released two albums, but after completing a third album, their record label declined to release it, and she left the group shortly thereafter. Her disappointment with Wild Orchid led to an addiction to crystal methamphetamine. In September 2006, Ferguson talked with Time about quitting her crystal meth addiction. "It was the hardest boyfriend I ever had to break up with," she says. "It's the drug that's addicting. But it's why you start doing it in the first place that's interesting. A lot of it was being a child actor; I learned to suppress feelings."

In 2003, Ferguson took over the lead female vocal duties for the Black Eyed Peas, replacing background singer Kim Hill, who had left the group in 2000. Ferguson recorded five songs with the group before she was invited to join them permanently. Ferguson's addition to the band, which had enjoyed underground success until then, helped them quickly grow into mainstream popularity.

In 2005, Ferguson inadvertently urinated on stage during a performance at San Diego's Street Scene festival. Ferguson later commented on the incident: "I had a few drinks before the show, but I didn't think to go to the bathroom before we went onstage. We were jumping around...and my bladder just started."

In December 2007, Blender picked Ferguson as their woman of the year.

Solo career

The Dutchess

After two successful Black Eyed Peas albums, Ferguson began pursuing a solo career. Her first album, released on September 19, 2006, was entitled The Dutchess. The album's name is a misspelled variant of the former title of Sarah Ferguson, the Duchess of York, with whom Ferguson shares a surname and popular nickname. The solo deal does not mean the demise of the Black Eyed Peas, as Ferguson intends to remain with the group, alternating between the two duties. The Dutchess is similar in style to that of the Black Eyed Peas, as fellow Peas member will.i.am is the album's executive producer.

Ferguson has had five hit songs from The Dutchess, with "London Bridge", "Glamorous", and "Big Girls Don't Cry" becoming number one singles. Her second single, "Fergalicious", peaked at #2. "London Bridge" reached #2 on the United World Chart, while "Fergalicious" and "Glamorous" both made it to #4. "Big Girls Don't Cry" became Ferguson's first worldwide #1 single, and is her most successful single to date. "Clumsy" was announced as the fifth single from The Dutchess after the major international success of "Big Girls Don't Cry". Ferguson has received her fifth Top 5 solo track from The Dutchess after "Clumsy" earned at #5 position on the Billboard Hot 100, on 22 December 2007.

On November 18, 2007, Ferguson won the Pop or Rock "Favorite Female Artist" at the American Music Awards.

Concert for Diana

Ferguson appeared at Wembley Stadium on 1 July 2007, performing "Glamorous" and "Big Girls Don't Cry" in a concert for the late Princess Diana put on by her two sons Prince William and Prince Harry; the DVD of the concert was released 5 November 2007.

Second studio album

Her producer, will.i.am, confirmed that the new album is half done. Despite claims that Ferguson will release her second album in March 1, 2008, in an interview with Ryan Seacrest for KIIS FM on 5 December 2007, she stated that she would still be focusing on her highly successful debut and that there was "nothing yet" on her new album.