It is essentially a suburb of Brussels and was a component of the short-lived Arrondissement of Brussels-Periphery, although it does not directly adjoin any part of the Brussels-Capital Region.

Wezembeek-Oppem is the only one of these that does not border Brussels directly since a narrow strip of land belonging to the neughbouring municipality of Kraainem lies in between the closest city boundary at Stockel (Woluwe-Saint-Pierre).

In 1993, when Belgium was turned into a federation, the municipality was included in the newly established Flemish Region.

During the Nazi German occupation in the Second World War, Wezembeek was the home of an orphanage set up by the Association of Belgian Jews [fr] (AJB), a Judenrat-like authority forcibly organised by the German occupational force and collaborating with the Nazis.

From August 1944, the AJB, under hard pressure of the Comité de Défense des Juifs, decided to hide the children until the end of the occupation.