The town was first established by Agustín Eguren as Edén Argentino ("Argentine Eden"), a bedroom community, in 1873.

Its population remained in the few hundreds until, in 1890, the Buenos Aires Great Southern Railway inaugurated a rail yard in the adjoining Villa Galíndez, to the east; La Fraternidad, one of Argentina's first and oldest trade unions, was founded by workers at the site in 1887.

Further such installations opened by Eliseo Ramírez and the Ramírez de Lafuente family in 1901 made the area a prime rail operations hub, and the Great Southern inaugurated its first commuter station there in 1902.

The town became home to a sizable community of Italian Argentines in the subsequent years, and prominent among these was Luis Máspero, who operated one of the country's largest hat factories, and Víctor Marangoni, owner of an important metalworks establishment; the Italian Mutual Insurance and Assistance Company was established here in 1913.

Remedios de Escalada was formally declared a city by the Buenos Aires Province Legislature in 1974.