Through the Righteous Babe Foundation, DiFranco has backed grassroots cultural and political organizations supporting causes including abortion rights and LGBT visibility.

[8] DiFranco released a memoir, No Walls and the Recurring Dream, on May 7, 2019, via Viking Books[9] and made The New York Times Best Seller list.

[15] DiFranco started playing Beatles covers at local bars and busking with her guitar teacher, Michael Meldrum,[16] at the age of nine.

In September 1995, DiFranco participated in a concert at the Rock and Roll Hall of Fame in Cleveland Ohio, inaugurating the opening of the Woody Guthrie Archives in New York City.

She later released a CD on Righteous Babe of the concert Til We Outnumber Em featuring artists such as DiFranco, Billy Bragg, Ramblin' Jack Elliott, Arlo Guthrie, Indigo Girls, Dave Pirner, Tim Robbins, and Bruce Springsteen with 100 percent of proceeds going to the Woody Guthrie Foundation and Archives and the Rock and Roll Hall of Fame Museum educational department.

[19] The 1990s were a period of heightened exposure for DiFranco, as she continued playing ever larger venues around the world and attracted international attention of the press, including cover stories in Spin, Ms., and Magnet, among others,[20] as well as appearances on MTV and VH1.

Her playfully ironic cover of the Bacharach/David song "Wishin' and Hopin'" appeared under the opening titles of the film My Best Friend's Wedding.

[21] She guest starred on a 1998 episode of the Fox sitcom King of the Hill, as the voice of Peggy's feminist guitar teacher, Emily.

[22] Beginning in 1999, Righteous Babe Records began releasing albums by other artists including Sara Lee, Sekou Sundiata, Arto Lindsay, Bitch and Animal, That One Guy, Utah Phillips, Hamell on Trial, Andrew Bird, Kurt Swinghammer, Buddy Wakefield, Anaïs Mitchell and Nona Hendryx.

[24] Since her 2005 release Knuckle Down (co-produced by Joe Henry) DiFranco's touring band and recordings have featured bass player Todd Sickafoose and in turns other musicians such as Allison Miller, Andy Borger, Herlin Riley, and Terence Higgins on drums and Mike Dillon on percussion and vibes.

In 2009, DiFranco appeared at Pete Seeger's 90th birthday celebration at Madison Square Garden, debuting her revamped version of the 1930s labor anthem "Which Side Are You On?"

"[29] In a 2019 interview with Jezebel, she stated that she preferred the term "queer" because "bisexual" "always sounded very medical, like something you do to a frog in 9th grade science or something", and further added that "the irony is I'm pretty fuckin' hetero, which is unfortunate for me because many of my deepest connections are with women.

I think religion serves a lot of different purposes in people's lives, and I can recognize the value of that, you know, the value of ceremony, the value of community, or even just having a forum to get together and talk about ideas, about morals – that's a cool concept.

But then, of course, institutional religions are so problematic.DiFranco has spoken critically of cancel culture, saying it is "just gonna get us nowhere" and "The human family can't divorce each other".

[45] On July 21, 2006, DiFranco received the Woman of Courage Award at the National Organization for Women (NOW) Conference and Young Feminist Summit in Albany, New York.

While primarily an acoustic guitarist she has used a variety of instruments and styles: brass instrumentation was prevalent in 1998's Little Plastic Castle; a simple walking bass in her 1997 cover of Hal David and Burt Bacharach's "Wishin' and Hopin'"; strings on the 1997 live album Living in Clip and 2004's Knuckle Down; and electronics and synthesizers in 1999's To the Teeth and 2006's Reprieve.

She developed a deep association with folksinger and social activist Utah Phillips throughout the mid-1990s, sharing her stage and her audience with the older musician until his death in 2008 and resulting in two collaborative albums: The Past Didn't Go Anywhere (1996) and Fellow Workers (1999, with liner notes by Howard Zinn).

[52] The Past is built around Phillips's storytelling, an important part of his art that had not previously been documented on recordings; on the album, DiFranco provides musical settings for his speaking voice.

[51] The followup, Fellow Workers, was recorded live in Daniel Lanois's Kingsway Studio in New Orleans and features Phillips fronting DiFranco's touring band for a collection of songs and stories.

Many of her songs are concerned with contemporary social issues such as racism, sexism, sexual abuse, homophobia, reproductive rights, poverty, and war.

Offers to play at colleges started coming in and her popularity grew largely by word of mouth and through women's groups or organizations.

In a 1997 open letter to Ms. magazine[63] she expressed displeasure that what she considers a way to ensure her own artistic freedom was seen by others solely in terms of its financial success.

In 1998, she was a featured performer in the Dead Man Walking benefit concert series[64] raising money for Sister Helen Prejean's "Not in Our Name" anti-death penalty organization.

DiFranco's commitment to opposing the death penalty is longstanding; she has also been a long time supporter of the Southern Center for Human Rights.

In 2010, after the Deepwater Horizon oil spill, she performed at the "For Our Coast" benefit concert joining Marianne Faithfull, C. C. Adcock and others at the Acadiana Center for the Arts Theater in Lafayette, raising money for Gulf Aid Acadiana, and the Gulf Aid show with Lenny Kravitz, Mos Def, and others at Mardi Gras World River City in New Orleans, both shows raising money to help protect the wetlands, clean up the coast and to assist the fishermen and their families affected by the spill.

The organization provides free marching band instruction to children in the New Orleans area in addition to academic tutoring and mentoring.

As an honored guest she marched in the front row for the three-mile route, along with Margaret Cho, Janeane Garofalo, Whoopi Goldberg, Gloria Steinem and others.

[78] Scot Fisher, formerly Righteous Babe label president and DiFranco's manager for many years, has been a longtime advocate of the preservation movement in Buffalo.

In 2006, the building opened its doors again, first briefly as "The Church" and then as "Babeville," housing two concert venues, the record label's business office, and Hallwalls Contemporary Arts Center.

[80] In October 2023, DiFranco signed an open letter to Joe Biden, President of the United States, of artists calling for a ceasefire of the Israeli bombardment of Gaza.