Sayre Avenue begins at 22nd Street in the Little Italy neighborhood on the city's near west side. It runs to the north in a diagonal direction for approximately one mile, intersecting Taylor Street, Roosevelt Road, and Randolph Street. The street becomes North Sayre Avenue upon intersecting Jackson Boulevard, and continues north all way to the Chicago River, where it ends.
Sayre Avenue is a commercial and residential street. The area is known for its Italian-American heritage and culture, and there are many Italian-American businesses and restaurants along the street. There are also several historical landmarks in the area, including the Hull House, the University of Illinois at Chicago, and the Jane Addams Memorial Park.