The history of Merksem goes back to Gallo-Roman times. During that period the region was mentioned as Merk (border) and Heim (settlement) being part of the dioceseKamerijk. Merksem has for centuries been part of a larger community together with Schoten and Sint-Job-in-'t-Goor. In the 16th century Merksem was separated from Schoten.
The road currently known as Bredabaan (Breda Road), once a major northern access to Antwerp, begins in Merksem and goes up north, all the way up until the border with The Netherlands. It ends in the Dutch village of Breda (hence the name). Other major axis-es would include Lambrechtshoekenlaan, Groenendaallaan, Maantjessteenweg and Ringlaan. Together with Bredabaan they could be considered as the boundaries of the centre of Merksem. Another suburb's main axis is a canal called: Albert Canal, which connects the Port of Antwerp to the river Maas and is an important component for freight traffic over water.