Isabelo de los Reyes was born to Elías de los Reyes and Leona Florentino in Vigan, Ilocos Sur. His mother, of mixed Spanish and Filipino descent, is recognised as the first significant female poet of the Philippines for her works in both Spanish and Ilocano. de los Reyes may have been distantly related to Ventura de los Reyes, a creole merchant who was the first Philippine delegate to the Spanish Cortes through his father's side. He may also have been a "distant cousin" of Jose Rizal through a Chinese tax collector married to both Rizal's grandmother and de los Reyes' grand-aunt.