After graduating from Northwestern University, Hughes moved to New York and in 1995 started a job as an intern at The Paris Review before being hired there full-time later that year.[2]
For three years she served as managing editor.[5] After the death of editor George Plimpton, Hughes became editor[3] and continued its tradition of accepting unsolicited submissions (the 'slush pile') as an important part of the role of smaller journals to promote new writers.[3][6] Hughes left the position after only one year, when the (newly created) Board of Directors did not renew her contract,[5][7] appointing Philip Gourevitch.[8][9]
After leaving The Paris Review, Hughes founded A Public Space, a nonprofit quarterly English-language literary and arts magazine based in New York City, in 2006.[10] Under Hughes' editorship, A Public Space has gained a reputation for spotting and publishing writers before they become widely known – two-time National Book Award winner Jesmyn Ward's first published short story, "Cattle Haul," appeared in A Public Space in January 2008.[11][12] Leslie Jamison, Nam Le, Jamel Brinkley, and Jamil Jan Kochai also debuted in the magazine. Hughes rediscovered the work of Bette Howland[13] and the writing of filmmaker Kathleen Collins.[14]
In 2007, Hughes was co-curator with Peter Conroy and Jake Perlin of the Between the Lines arts festival at the Brooklyn Academy of Music.[15] She is a frequent speaker and panelist at literary conferences, including the Lannan Foundation[16] and PEN America.[17]
In 2012, Hughes became a contributing editor to Graywolf Press[18] and A Public Space launched a partnership with the press to publish books by the magazine's contributors. In 2019, A Public Space launched an independent book imprint, A Public Space Books.
Hughes has received the PEN/Nora Magid Award for Editing and the CLMP Award for Paradigm Independent Publishing. In 2018, A Public Space received the inaugural Whiting Literary Magazine Prize, with the judges' citation recognizing the magazine as "a gorgeously curated collection we experience as a cabinet of wonders."
Hughes teaches in Columbia University's MFA program.