Fusco's work explores gender, identity, race, and power through performance, video, interactive installations, and critical writing.

She began traveling to Cuba and participating in the visual arts scene there, until in the mid-1990s she withdrew as a result of post-Cold War political and cultural changes in the country.

[9] Fusco also engages with legacies of Cuban exile in her work, as in some of her earlier performances where she stages Catholic rituals and experiences of dislocation.

[10] In 1992 Fusco created the influential performance piece Two Undiscovered Amerindians Visit the West in collaboration with Guillermo Gómez-Peña.

[1] During performances of Two Undiscovered Amerindians..., Fusco and Gómez-Peña put themselves on public display in a cage, in a satirical reference to the historical practice of exhibiting human beings as entertainment.

[12] The work was a critique of colonialism, specifically of the role played by the scientific institutions in which it was performed, and a response to the global quincentenary celebrations of Christopher Columbus's arrival in the Americas.

[26] In it, Fusco centers the aesthetic and cultural value of artistic expression and works against notions of reducing Latin American performance to "the political".

[27] English Is Broken Here: Notes on Cultural Fusion in the Americas (1995) was her first collection of interviews and essays, for which she won the 1995 Critics' Choice award.

In 2014 she received a Fulbright appointment and served as the Distinguished Chair in the Visual Arts at Fundação Armando Alvares Penteado in São Paulo, Brazil, for one year.