The San Diego Union-Tribune voted Del Rio one of the "Top 10 Singers in San Diego", after which she moved to Los Angeles in 1989 to further develop her career. After recording the song "Llorando", a Spanish-language version of Roy Orbison's "Crying", she moved to Nashville in 1994. There, she was signed to Irving Azoff's label, Giant Records, and recorded her first album, Nobody's Angel. The title track was released on a compilation album and made it to No. 2 on the singles charts in the Netherlands.
Her vocals can be heard on numerous soundtracks such as Sin City, Streets of Legend, Man on Fire, and Mia Sarah. Del Rio made a notable cameo appearance in David Lynch's 2001 film Mulholland Drive, singing "Llorando" a cappella. She is also featured in Richard Kelly's film Southland Tales, providing solo vocals in a string arrangement of "The Star-Spangled Banner". She performed the song "No Stars", written in collaboration with David Lynch and John Neff, at the end of Part 10 of Twin Peaks: The Return. Joining Del Rio on stage was the musician Moby on guitar.
