His fine art photography has been shown internationally in over 100 exhibitions and is in the collections of the Baltimore Museum of Art and the Inter-American Development Bank. Villarrubia identifies as LGBT+ and Hispanic/Latino. As an illustrator he is best known for his collaborations with Alan Moore (Promethea, Voice of the Fire and The Mirror of Love), Richard Corben (CAGE, Starr, Conan) and Paul Pope (Batman Year 100, 2007 Eisner Award for "Best Limited Series"). In 2010, he worked on the story featured in Unknown Soldier issues #13-14, with Joshua Dysart and Pat Masioni. The story won the prestigious Glyph Comics Award for Story of the Year. The Glyph Comics Awards recognize the best in comics made by, for, and about people of color. He won the 2017 Carlos Giménez Award for Best Spanish Colorist. He colored the first five issues of America, the first LatinX LGBT+ Marvel superhero. It was written and drawn by an entire Hispanic team that included two members of the LGBT+ community, the writer Gabby Rivera and Villarrubia. It was nominated for a 2017 GLAAD Award. Also, in 2017 he worked with writer Sarah Vaughn and Filipino artist Lan Medina in Deadman: Dark Mansion of Forbidden Love. It featured the first non-binary African-American character in a DC Comics publication. It was also nominated for a GLAAD Award.

The first series that he edited, Infidel, featuring two BIPOC female protagonists, is being turned into a film by  Michael Sugar and TriStar. DC Comics' prestige imprint Black Label announced two series colored by Villarrubia to be launched in November 2020, Sweet Tooth: The Return, where he reunited with collaborator Jeff Lemire and The Other History of the DC Universe, written by John Ridley.