Antoni was born in the United States of Trinidadian parents and grew up largely in the Bahamas, where his father practised medicine. He says his "fictional world" is "Corpus Christi", the invented island (based on Trinidad) that he introduced in his first novel, Divina Trace (1991).
Antoni studied at Duke University and in the creative writing programme at Johns Hopkins University before joining the Iowa Writers' Workshop at the University of Iowa, where he began working on Divina Trace. He has said that he spent a total of ten years completing the novel, which won the Commonwealth Writers Prize for best first novel in 1992.
Antoni lived for a time in Barcelona and taught at the University of Miami from 1992 to 2001. In 2004 he began teaching at Barnard College, Columbia University and The New School.