Archaeological finds on the Lokeren territory prove that this area was populated in Neolithic times. A Roman road ran along the Durme river. The name Waas was given to this area by the Romans from the Germanic root Wasu meaning "marshy land". The first mention of the name Lokeren, however, dates from 1114. Unlike the older settlements, the new village came to be built on the right bank of the Durme. By the middle of the 12th century, it had become an independent parish, with agriculture and flax as the two main drivers of the economy. The textile industry would remain important until well into the 20th century.
Until the 1970s, haircutting (an industrial practice of cutting hair from rabbit skins to make felt, a basic material for hat makers) and slaughterhouses were among Lokeren's main industries. Today, the city enjoys a more varied economical and cultural infra-structure.