Hawkins's debut album, Tongues and Tails, was released in 1992. It achieved both worldwide commercial success and critical acclaim, earning her a Grammy nomination for Best New Artist in 1993. The single "Damn I Wish I Was Your Lover" went to #5 on the Billboard Hot 100 singles chart in the USA and was also a Top 20 hit in the UK. Hawkins was asked to perform Bob Dylan's "I Want You," which she covered on Tongues and Tails, for the 1992 Madison Square Garden concert honoring Dylan's 30th anniversary as a musician; this was later released as The 30th Anniversary Concert Celebration.

In 1994, Hawkins posed nude for Interview magazine. As she explained to Ed Rampell when he interviewed her for Q magazine, she met the Photographer, Bruce Weber, and was asked if she could do a photo shoot with him. She had her own clothes when she showed up to the photo session, but he had a dress he wanted her to try on. She did not think it looked very good on her. It got to the point where she was only wearing a coat, and Weber suggested she remove that too. By this stage, she was not even thinking about how she looked as she felt quite comfortable with him. Weber later told her that giving her the unflattering dress was part of his plan to get her naked.

Also in 1998, Hawkins's record company at the time, Sony Music, delayed the release of her third album. Its executives were unhappy with the finished product and wanted Hawkins to rework some of the material. In particular, they insisted that Hawkins remove a banjo track from one of the songs. Hawkins refused to accommodate them, citing artistic integrity as her main reason. After a lengthy battle between Hawkins and the company, the album, Timbre, was eventually released in 1999, though Sony declined to promote it. Hawkins subsequently left the label and founded her own label, Trumpet Swan Productions. In 2001, Timbre was re-released on Hawkins's label, now as a two-disc set that contained new songs, demos, remixes, and videos. Her first independently recorded and released album, Wilderness, was released in 2004.

In August 2007, Hawkins headlined the first Los Angeles Women's Music Festival in support of its dual agenda of supporting animal rescue groups and promoting and supporting female Musicians. Hawkins is a vegan and a long-time supporter of animal rights.

In February 2008, Hawkins re-recorded her hit "Damn I Wish I Was Your Lover" as "Damn, We Wish You Were President" in support of presidential candidate Hillary Clinton. Hawkins also wrote in her blog, "Hillary Clinton's achievements come from her heart. She has initiated so much positive change for families, children, victims of crime and the environment in her struggle for the forward movement of America and the working people of this nation."

In May 2010, Hawkins began supporting Waterkeeper Alliance, an organization of on-the-water advocates who patrol and protect more than 100,000 miles of rivers, streams and coastlines in North and South America, Europe, Australia, Asia and Africa. She donated 100% of the proceeds of her single "The Land, the Sea, and the Sky" to the organization.

In February 2011, Hawkins performed at the Big Gay Party event staged by GOProud, an organization of gay conservatives, as part of the year's Conservative Political Action Conference festivities. In an after-show interview in the reason.tv documentary "Liberal in Bed, Conservative in the Head: Sophie B. Hawkins." Hawkins gave her views on issues such as gun ownership, the free market, limited government and identity politics.

In an interview with Rock Cellar Magazine in 2012, Hawkins said that she identified as omnisexual. Although there were rumors she had dated Martina Navratilova and Jodie Foster, she denied those, saying, "I've never met any of the women I'm supposed to have had affairs with."

On April 4, 2013, Sophie appeared on the TV series Community as herself, performing "Damn I Wish I Was Your Lover" and "As I Lay Me Down" during the community college's "Sophie B. Hawkins Dance," so named because one of the characters confused the singer with Susan B. Anthony and Sadie Hawkins.