The Great Lakes region of North America is a binational Canadian–American region centered around the Great Lakes that includes eight U.S. states (Illinois, Indiana, Michigan, Minnesota, New York, Ohio, Pennsylvania, and Wisconsin) and the Canadian province of Ontario. Canada´s Quebec province is at times included as part of the region because the St. Lawrence River watershed is part of the continuous hydrologic system. The region forms a distinctive historical, economic, and cultural identity. A portion of the region also encompasses the Great Lakes megalopolis.

State and provincial governments are represented in the Conference of Great Lakes and St. Lawrence Governors and Premiers, which also serves as the Secretariat to the Great Lakes St. Lawrence Compact and the Great Lakes–Saint Lawrence River Basin Sustainable Water Resources Agreement.

The Great Lakes region takes its name from the corresponding geological formation of the Great Lakes Basin, a narrow watershed encompassing the Great Lakes, bounded by watersheds to the region's north (Hudson Bay), west (Mississippi), and east and south (Ohio, part of the Mississippi watershed). To the east, the rivers of St. Lawrence, Richelieu, Hudson, Mohawk and Susquehanna form an arc of watersheds east to the Atlantic.

The Great Lakes region, as distinct from the Great Lakes Basin, defines a unit of sub-national political entities defined by the U.S. states and the Canadian province of Ontario encompassing the Great Lakes watershed, and the states and province bordering one or more of the Great Lakes.