His novel Doña Bárbara was first published in 1929 and it was because of the book's criticisms of the regime of longtime dictator Juan Vicente Gómez that he was forced to flee the country.

President Gallegos initiated the implementation of an "open-door" policy, which sparked an influx of Italians, eventually becoming the largest European population group within Venezuela.

Nevertheless, army officers Carlos Delgado Chalbaud, Marcos Pérez Jiménez and Luis Felipe Llovera Páez overthrew him in the 1948 Venezuelan coup d'état in November of that year.

He was nominated for the Nobel Prize in Literature in 1960, largely due to the efforts of Miguel Otero Silva and gained widespread support in Latin America,[9] but ultimately lost out to Saint-John Perse.

The Rómulo Gallegos International Novel Prize was created in his honor on 6 August 1964 by a presidential decree, enacted by Venezuelan president Raúl Leoni.

The declared purpose of the prize is to "perpetuate and honor the work of the eminent novelist and also to stimulate the creative activity of Spanish language writers."