The song was written in 1942[3] for Estrada's brother who had been deployed to Panama during World War II and was feeling nostalgia for his Puerto Rico motherland.

Two later interpretations achieved large popularity as well as measured by radio ratings: those of Manuel Jiménez Quartet (RCA Víctor, 1948) and the one by Joe Valle with Moncho Usera and his orchestra (Seeco, 1949).

[9] "En mi Viejo San Juan" is considered a classic and has been performed by numerous artists.

[10] Originally interpreted by El Trío Vegabajeño,[11] the song would later be interpreted by artists like Luis Miguel,[12] Javier Solis,[13][14][15]Vikki Carr,[16] Danny Rivera,[17] Marco Antonio Muñiz,[18] Trío Los Panchos,[19] Rafael Cortijo,[20] Ismael Rivera,[21] Celia Cruz,[b] and Rocío Dúrcal,[citation needed] plus "hundreds of other voices including Libertad Lamarque, Marco Antonio Muñiz, Ginamaría Hidalgo, and Felipe Pirela.

"En mi Viejo San Juan" has been recorded by American, Russian, German, French, Japanese orchestras, among others.

[29] The 1988 Tato Laviera's "Mainstream Ethics" poem uses most of the lyrics of En mi Viejo San Juan to depict the Puerto Rican "revolving door" migration motif.