She has participated in activism and community organizing for a range of causes, and served as the first executive director for the Transgender Gender Variant Intersex Justice Project.

[2][3][4] She was raised on the South Side of Chicago, while her father worked for the post office and her mother managed a beauty shop.

[5] She has described working as a showgirl at the Jewel Box Revue in Chicago and New York,[3] and how she developed her name to add "Griffin" to honor her mother.

[5] In a 2014 interview with the Bay Area Reporter, Griffin-Gracy said that after moving to New York City, she found the Stonewall Inn "provided us transwomen with a nice place for social connection" and that few gay bars otherwise allowed entry to trans women at the time.

[7][5] In 2004, Griffin-Gracy began working at the Transgender Gender Variant Intersex Justice Project (TGIJP),[2] shortly after it was founded by Alex Lee.

[10] She became the executive director of the organization, which is focused on providing support services to transgender, gender variant, and intersex people in prison.

[2][5][11] Her work included visiting trans women and men in California prisons to help coordinate access to legal and social services, and testimony at the California State Assembly and United Nations Human Rights Committee in Geneva about human rights violations in prisons.

"[2] In 2013, she was part of a campaign to revise wording on a Stonewall commemorative plaque; she advocated for "inclusive language to honor the sacrifice we as trans women displayed by taking back our power.

[8] In May 2023, Verso Books published Miss Major Speaks: Conversations with a Black Trans Revolutionary, a memoir composed of interviews with Griffin-Gracy by journalist Toshio Meronek.

[19][20] In the memoir Griffin-Gracy reflects on her early life, education, experience as a sex worker, the 1969 Stonewall rebellion,[19] incarcerations, knowing Frank "Big Black" Smith as a mentor, and her years of activism and community organizing, including during the AIDS epidemic in the 1980s, as well as her work as the director of the Transgender Gender Variant Intersex Justice Project (TGIJP).

[3][20][19] In a review for Gender & Development, Haley McEwen writes, "Beyond an opportunity to learn about the life of a leader and elder in the Black transgender community through vivid personal accounts of activism and survival, listening to Miss Major speak is to subvert systems that have worked to erase and silence Black transgender women throughout history and in present reality.

[...] In some ways, this book is a new version of the community building and emotional support that is Miss Major’s life’s work.