The district's name originated from a station of the Central Argentine Railway (today part of the Mitre Line) called "km 14". In 1907, it received the name of "Pueyrredón" in honour of the illustrious Brigadier Juan Martín de Pueyrredón. Since the railroad provided the area with its main transportation connections, the station became the neighbourhood's official namesake, and "Villa Pueyrredón" was established in 1923.
The population in this neighbourhood was established by European settlers, principally Italian and Spanish, as well as Lebanese, all of whom arrived in the late 19th and early 20th centuries to be employed at the "great railway project" (the most important in Latin America). The large number and variety of small businesses established by these communities gave the neighborhood a very particular and ethnically diverse character.