The district owes its name to Dr. Pedro Luro, a prominent local physician and real-estate developer who, during the 1870s, sold most of his property in the area as residential lots.

The neighborhood, which at the time was on the outskirts of the city, grew rapidly following the inaugural in 1911 of the Buenos Aires Western Railway's Villa Luro station (today a stop along the Sarmiento Line).

The district's largest park, Plaza Ejército de los Andes, was opened in 1939.

A defunct Western Railway line that divided the neighbourhood diagonally was converted into the Avenida del Justicialismo in 1951, and this avenue was in turn replaced by the Perito Moreno Expressway in 1980.

Villa Luro is also accessible from downtown Buenos Aires (11 kilometres (7 mi) to the east) via Rivadavia Avenue, and most of the high-rises in the largely low-density district were built along it.