[11] Castillo first became interested in acting in the third grade, after seeing his older brother in a school production of The Wizard of Oz as the Tin Woodman.

[5] While in sixth grade at Our Lady of Sorrows Catholic School, Castillo met and befriended future Mutemath bass guitarist Roy Mitchell-Cárdenas.

[7][13] Later, in high school, they started an underground punk-rock band called IPM (short for "Influential Phecal Material") together with their friends Nick Trevino and Robert Vleck.

[3][15] His first acting role was in a high school production of Paul Zindel's play The Secret Affairs of Mildred Wild.

[18] It was then, at age 14, that he met and became friends with future staff writer for Devious Maids, Girls and Looking, Tanya Saracho, who also attended McAllen High School.

[12] Castillo also found inspiration from several Hispanic artists in the media, including Miguel Piñero, and an anthology of works from the Nuyorican Poets Cafe.

[9] He looked up to several actors, such as Al Pacino and Anthony Quinn, as icons, and spent much of his time watching the film The Outsiders.

[12] After graduating high school, Castillo went on to study playwriting as an undergraduate at Boston University College of Fine Arts,[3][17] though he continued to act, and majored in theater.

[15] His performance as Beto in the Ensemble Studio Theatre's 2008 production of José Rivera's Flowers was described as "flawlessly nuanced" by Laura Collins-Hughes of The New York Sun.

[15][26] Castillo also appeared in the 2012 BareBones production of Jesus Hopped the 'A' Train in Pittsburgh, the inaugural performance of which was directed by Philip Seymour Hoffman for the LAByrinth Theater Company.

[29][30] He starred alongside Sandra Oh in the role of Gerardo in the 2014 Victory Gardens Theater production of Death and the Maiden,[15] which was well received by critics.

[32] Death and the Maiden was originally produced on Broadway with Glenn Close, Richard Dreyfuss, and Gene Hackman, but Latino actors such as Castillo felt undervalued when ethnic characters were not cast in a play by a Chilean playwright.

His role in the 2011 independent film Cold Weather garnered favorable reviews and praise from critic Roger Ebert.

[36] During his acting career, Castillo has appeared in various TV roles, including shows such as Nurse Jackie, Blue Bloods,[10] and Law & Order.

In 2014, Castillo was cast in the HBO series Looking as Ricardo "Richie" Donado Ventura,[17][37] the love interest of main character Patrick, played by Jonathan Groff.

[15] To research his role as Richie, Castillo watched Looking executive producer Andrew Haigh's 2011 film Weekend.

[39][40] Critics particularly noted Castillo's portrayal of an openly gay Mexican-American man as a rare representation of the Latino-American community on television.

"[12] He told Out magazine that he hopes that his character on the show will both enlighten and educate straight audiences, as well as shed light on some of the experiences of the gay Latino community.

[41] In the show's second season, Castillo was added as a regular cast member alongside co-stars Groff, Frankie J. Álvarez, Murray Bartlett, Lauren Weedman, and Russell Tovey.

[12] In 2015, Castillo appeared as Eduardo Flamingo, the emotionless, unfeeling villain on Fox Broadcasting Company's drama series Gotham.

[39] Castillo's play, Knives and Other Sharp Objects, about class, race, and assimilation in South Texas, debuted at the Public Theater as part of LAByrinth's works in development in 2009.

Then I understood that this is what most of America is like, and that I grew up sheltered.Despite having a bicultural upbringing, Castillo stated that he always felt American growing up, and that he and his siblings were considered "gringos" when they visited Mexico.

[39] Castillo describes his childhood as sheltered from racism and racial dynamics in the US due to McAllen's high Hispanic and Latino population.

"[2] Before shooting the pilot for Looking, Castillo wrote a letter to his family to explain the part and make them aware of the more explicit aspects of the show.