It extends from the Notre-Dame-de-Bon-Secours Chapel on Saint Paul Street in Old Montreal to the bank of the Rivière des Prairies at the north end of the island. It is designated Route 335 from Sherbrooke Street to the Metropolitan Expressway, and is known as Bonsecours Street south of Saint Antoine Street. Along its length, it passes through the boroughs of Ville-Marie, Le Plateau-Mont-Royal, Rosemont–La Petite-Patrie, Villeray–Saint-Michel–Parc-Extension, and Ahuntsic-Cartierville.
Saint-Denis serves as one of the primary thoroughfares of both the Latin Quarter, where it plays host to a number of bars and restaurants, to the Plateau Mont-Royal, where it is known as one of the best places to view Montreal's distinct style of architecture. It becomes primarily a residential street north of the Metropolitan Expressway. The eastern portion of the Montreal Metro's Orange Line runs parallel to the street, two blocks to the east.
It is named for Saint Denis of Paris.
South of the Ville-Marie Expressway, the street crosses Old Montreal and is named rue Bonsecours. North of the Ville-Marie Expressway, it becomes Saint Denis Street and crosses the Quartier Latin. In the Quartier Latin, its vocation is primarily touristic and leisure-related, with restaurants and theatres located along this stretch. Near Saint Catherine Street, it crosses the downtown Université du Québec à Montréal (UQAM) campus while a little further north, it borders the Cégep du Vieux Montréal.
North of Sherbrooke Street, Saint Denis Street enters the borough of Le Plateau Mont-Royal. In the Plateau-Mont-Royal and Rosemont-La Petite-Patrie to the north, it is a commercial street lined with small stores. Parallel streets are mostly residential. To the west, Saint Laurent Boulevard also serves a commercial purpose.