[6] Machado's paternal grandfather left Santa Clara, Cuba, for the United States when he was 18, gaining U.S. citizenship after serving in the Korean War.

He then moved to D.C. and worked at the United States Patent Office, where he met Machado's grandmother, who came over to the U.S. from Austria after World War II.

[6] Machado grew up in a very religious United Methodist household; this upbringing, she says, led to a sense of guilt about her queer sexuality for several years.

[7] She attended Parkland High School in South Whitehall Township, Pennsylvania,[8] and then American University in Washington, D.C., graduating in 2008.

After a rejection from Starbucks in 2013, she took up work at Lush, a soap store, while she taught writing as an adjunct professor at Rosemont College and other schools in the area.

[1] Machado's short stories, essays, and criticism have been published in a number of magazines including The New Yorker, Granta, The Paris Review, Tin House, Lightspeed, Guernica, AGNI, National Public Radio, Gulf Coast, Los Angeles Review of Books, Strange Horizons,[12] and other publications.

An analysis by io9 indicated that if not for the Sad Puppies ballot manipulation campaign, Machado would have been a finalist for the 2015 John W. Campbell Award for Best New Writer.

[28] Her essay "Both Ways", about the 2009 film Jennifer's Body, is part of the anthology It Came from the Closet: Queer Reflections on Horror, published in October 2022.