The Great Lakes were formed approximately at the end of the Pleistocene period, when the glacier-carved lake basins were filled with meltwater from the retreating ice sheet. The lakes are connected to each other by straits, short rivers, and canals. The height above sea level of the lake surfaces varies from Lake Superior's 602 ft (183 m) to Lake Ontario's 246 ft (75 m); the greatest sudden drop occurs at Niagara Falls (167 ft/51 m) between lakes Erie and Ontario; the water levels fluctuate over the months and years due to climatic changes. All the lake bottoms, except that of Lake Erie, extend below sea level.

French traders were the first Europeans to see any of the Great Lakes; Étienne Brulé visited Lake Huron c.1612. In 1614, Brulé and French explorer Samuel de Champlain explored Lake Huron and Lake Ontario. In 1679, the French explorer La Salle sailed from Lake Erie to Lake Michigan. The Great Lakes region, rich in furs, was contested for many years by the French, English, and Americans. The close of the War of 1812 finally ended the struggle for possession of the Great Lakes, and settlement of the region rapidly followed. The opening of the Erie Canal in 1825 accelerated the development of commerce on the Great Lakes.

The opening of the St. Lawrence Seaway in 1959 made the Great Lakes a truly international water body. The Illinois Waterway connects the lakes with the Mississippi River and the Gulf of Mexico; the New York State Canal System (including the Erie Canal) joins the Great Lakes with the Hudson River and the Atlantic Ocean. Shipping on the lakes carries large quantities of iron ore and grain, coal, and petroleum, and manufactured articles from April until December, until ice closes most of the ports and winter storms hinder navigation. The large industrial lakefront cities include Toronto, Hamilton, Buffalo, Cleveland, Detroit, Gary, Milwaukee, and Chicago. Large concentrations of population and industry along the lakes' shores led to pollution, especially of Lake Erie, but the condition of the lakes has improved since the 1960s. The Great Lakes region, with its national parks and lakeshores, state parks, and many natural and scenic features, has become an important year-round recreation area.