Houston Street is a major east-west thoroughfare in downtown Manhattan, running crosstown across the full width of the island of Manhattan, from Franklin D. Roosevelt East River Drive (FDR Drive) and East River Park on the East River to Pier 40 and West Street on the Hudson River. It generally serves as the boundary between neighborhoods, with Alphabet City, the East Village, NoHo, Greenwich Village and the West Village lying to the north of the street, and the Lower East Side, most of the Bowery, Nolita and SoHo to the south.

The numeric street-naming grid in Manhattan, created as part of the Commissioners' Plan of 1811, begins immediately north of Houston Street with 1st Street at Avenue A, although the grid does not fully come into effect until 13th Street.

"Houston" is pronounced like a combination of the words "house" and "ton," and not like the city of Houston, Texas.