Established as Barracas al Sur on April 7, 1852, by Quilmes Justice of the Peace Martín José de la Serna, the town grew to become a major rail center during the late 19th century.

The city's largest employers are textile mills, meat-packing and grain-processing plants, oil refineries, metallurgical works, extensive docking facilities, and markets for farm and ranch products; some of the most prominent firms whose main facilities are in Avellaneda are food processor Molinos Río de la Plata, beverage maker Cepas Argentinas, bathroom fixtures maker Ferrum, and América 24 cable news.

Located on the banks of the Riachuelo, it was developed by Irish Argentine businessman Eduardo Casey and inaugurated in 1889; served by a Buenos Aires Western Railway rail link, the 150,000 m2 (1,600,000 sq ft) brick structure was at the time the largest warehouse in the world.

The decentralization of warehousing and wholesaling during the 20th century, as well as its nationalization in 1946 as part of the IAPI state export agency, resulted in its decline, however, and the Central Produce Market closed in 1963.

The construction of numerous high rises around Alsina Square during the 1950s and '60s led to irreparable structural damage to the cathedral, however, and in 1967 it was closed to the public.