Leigh has described her work as auto-ethnographic, and her interests include African art and vernacular objects, performance, and feminism.

[6] Simone Leigh was born in 1967 in Chicago, Illinois, to Jamaican immigrants who came to the United States as missionaries for the Church of the Nazarene.

Her neighborhood had become segregated by white flight beginning in the 1960s; nonetheless, she viewed the South Side of Chicago as a wonderful place for a black person to grow up.

[1] Although her parents wanted her to go to a stricter religious school and live at home, Leigh chose Earlham College, associated with the Quakers, in Richmond, Indiana.

[11] Her objects often employ materials and forms traditionally associated with African art, and her performance-influenced installations create spaces where historical precedent and self-determination co-mingle.

[22] The film Conspiracy, featured in her solo show at the Biennale, was co-produced with filmmaker and visual artist Madeleine Hunt-Ehrlich.

[11] Simone Leigh is the creator of the Free People's Medical Clinic a social practice project created with Creative Time in 2014.

[11] The installation was located in a 1914 Bed-Stuy brownstone called the Stuyvesant Mansion, previously owned by notable African-American doctor Josephine English (1920–2011).

As an homage to this history, Leigh created a walk-in health center with yoga, nutrition and massage sessions, staffed by volunteers in 19th-century nurse uniforms.

[50]Brick House is the inaugural commission for the High Line Plinth, a landmark destination for major public artworks in New York City since 2019, and is part of a series of art installations that will rotate every eighteen months[51] and the first space on the High Line dedicated solely to new commissions of contemporary art.

[5] The content of Leigh's sculpture directly contrasts the location in which it is sited in New York since it is situated where "glass-and-steel towers shoot up from among older industrial-era brick buildings, and where architectural and human scales are in constant negotiation.

[2] This exhibition honors Esmin Elizabeth Green, who died from blood clots after sitting in a waiting room of a Brooklyn hospital for 24 hours, and provides an alternative vision of health care shaped by female, African-American experience.

Outside of museum hours this exhibition became "The Waiting Room Underground" providing free, private workshops outside of the public eye, an homage to the healthcare work of the Black Panthers and the United Order of Tents.

[55] Additionally this exhibition featured lectures; workshops on self-defense, home economics, and self-awareness; Taiko drumming lessons for LGBTQ youth, and summer internships with the museum for teens.

[63] Her previous auction record, a life-size mixed media female head titled Birmingham (2012), was sold for $2.2 million at Sotheby’s in New York in 2022.