It is located in the southern part of the City of Brussels, on the border with the municipalities of Saint-Gilles and Ixelles, where it runs south–east from the Place Louise/Louizaplein [nl] to the Bois de la Cambre/Ter Kamerenbos, covering a distance of 2.7 km (1.7 mi).

[1][2] The Avenue Louise was first proposed in 1844 by two private property developers, Jean-Philippe De Joncker and Jean-Baptiste Jourdan, who submitted to the City of Brussels a plan for a monumental avenue bordered by chestnut trees that would allow easy access from Brussels' city centre to the popular recreational area of the Bois de la Cambre/Ter Kamerenbos.

[6] Originally, fierce resistance to the project was put up by the towns of Saint-Gilles and Ixelles—then, as now, separate municipalities (local authorities) from the City of Brussels—through whose territories the avenue was to run.

The Nazi security organisation, the Sicherheitspolizei-Sicherheitsdienst (Sipo-SD), of which the Gestapo was a part, set up their Brussels headquarters on the Avenue Louise.

[18] On 20 January 1943, Baron Jean de Sélys Longchamps, a Brussels-born fighter pilot in the Royal Air Force, mounted a solo attack on the headquarters at number 453.

The northern part is sunken and has three tunnels—all housed in the central lane, which was widened by the removal of two rows of trees—with level crossings and car parking spaces aboveground.

Although it attempted to remedy the discrepancies in the avenue's silhouette, the plan made no pronouncement on the allocation of the buildings, giving free rein to land speculation.

[23][26] At the end of the 1990s, the JNC International SA office, as part of the chemin de la ville project, studied the redevelopment of public spaces on the Avenue Louise, with the installation of new sculptures and lighting, and the redesign of pavements and surface parking areas.

It implies that no metro line runs through the avenue, despite its high built density and its multiple functions of shops/offices/housing,[28] the latter being in a way replaced by these tunnels.

With two tramway lines and thousands of cars sharing this narrow segment of the avenue, large traffic jams occur during rush hours.

However, construction was abandoned toward its end due to protests of local businesses fearing losses if patrons were to be diverted through a tunnel.