Although the area is known to have been inhabited since prehistoric times, the town is of relatively recent provenance, having been founded in 1704 by refugees from Gibraltar.

After abandoning their homes following Gibraltar's capture by Anglo-Dutch forces during the War of the Spanish Succession, some of the inhabitants of Gibraltar took refuge around the existing hermitage of San Isidro at the confluence of the rivers Guadarranque, Guadacorte and Cañas.

In 1717 the settlers were ordered to concentrate themselves at Los Barrios and the neighbouring communities of Algeciras and San Roque (Cádiz).

The three communities had a single administration at San Roque until undergoing a three-way split in 1756.

Los Barrios was principally an agricultural and fishing district until the Francisco Franco era; it is now heavily industrialised.