The city is divided into 79 neighborhoods. The divisions have no legal standing, although some neighborhood associations administer grants or hold veto power over historic-district development. Nevertheless, the social and political influence of neighborhood identity is profound. Some hold avenues of massive stone edifices built as palaces for heads of state visiting the 1904 World's Fair. Others offer tidy working-class bungalows, loft districts, or areas hard-hit by social problems and unemployment. Many of them have retained - quite consciously and deliberately - a camaraderie missing from many American towns today.

St. Louis also possesses several distinct examples of 18th and 19th century architecture, such as the Soulard Market district (1779-1842), the Chatillon-de Menil House (1848), the Bellefontaine Cemetery (1850), the Robert G. Campbell House (1852), the Old Courthouse (1845-62), the original Anheuser-Busch Brewery (1860), and two of Louis Sullivan's early skyscrapers, the Wainwright Building (1890-91) and the Union Trust Building.

Among the best-known, architecturally significant, or well-visited neighborhoods are, Benton Park, Carondelet, the Central West End, Clayton/Tamm (Dogtown), Dutchtown South, Forest Park Southeast, Grand Center, The Hill, Lafayette Square, Shaw (home to the Missouri Botanical Garden and named after the Garden's founder, Henry Shaw), Southwest Garden, Soulard (home of the second-largest Mardi Gras festival in the nation), Tower Grove East, Tower Grove South, Hortense Place (home to many grand mansions) and Wydown/Skinker.

The Hill  is an historically Italian neighborhood where many of the area's best Italian restaurants can be found. The Hill was the home of Yogi Berra and many other noted baseball players. In the 1800’s, Italian immigrants worked the area’s clay mines, and built small bungalows to house their families. Today, the area retains row upon row of almost-touching bungalows up and down the streets, virtually defining the neighborhood known as The Hill.

Dogtown,  is the unofficial name of the area called Forest Park Southwest. There are several stories about the origin of the name, the favorite being that dog-eating Igorot tribesmen on display at the 1904 World’s Fair did their hunting there.

Central West End,  developed around the turn of the century, is home to some of St. Louis’ most historic residences. Opulent and grand in scale, these homes were the epitome of elegance, one having so much marble detailing that it took workmen two full years to install it.

Soulard, with its brick row houses and ornate wrought iron, is a little bit of old Europe in the near south side. The Soulard Farmer’s Market features an eclectic array of food—from freshly caught channel catfish to exotic spices and decorative vegetables. Low prices attract gourmet and fixed-income shoppers alike, and on any given Saturday, up to 20 different languages can be heard as customers wind their way through rows of stands.

Lacledes Landing,  located on the Mississippi Riverfront directly north of the historic Eads Bridge, is popular for its restaurants and nightclubs, turn-of-the-century cobblestones and horse-drawn carriages.