Often confused with Park Hill, Cole, or the City Park neighborhoods, Clayton is a distinct neighborhood as defined by the city of Denver. The neighborhood is named for the historical former George W. Clayton Trust and College located on the northwest corner of Martin Luther King Blvd. and Colorado Blvd.

Clayton is bounded by York Street on the west, Colorado Blvd. on the east, Martin Luther King Blvd on the south and 40th Street on the north.