Casco Bay is an open bay of the Gulf of Maine on the coast of Maine in the United States. The National Oceanic and Atmospheric Administration's chart for Casco Bay marks the dividing line between the bay and the Gulf of Maine as running from Bald Head on Cape Small in Phippsburg west-southwest to Dyer Point in Cape Elizabeth. The city of Portland and the Port of Portland are on Casco Bay's western edge.

There are multiple theories about the origin of the name "Casco Bay". Aucocisco, an Anglicisation of the Abenaki name for the bay, means "place of herons", "marshy place", or "place of slimy mud". The explorer Estêvão Gomes mapped Maine's coast in 1525 and named the bay "Bahía de Cascos", translated as "Bay of Helmets", based on its shape.

Colonel Wolfgang William Römer, an English military engineer, reported in 1700 that the bay had "as many islands as there are days in the year" leading to the bay's islands being called the Calendar Islands, based on the popular myth there are 365 of them. Estimates vary on the actual count, with the Casco Bay Estuary Partnership listing 785 if including exposed ledges. Former Maine state historian Robert M. York said there are "little more than two hundred" islands in Casco Bay.

Casco Bay spans about 229 square miles, with its shore stretching 578 miles by one estimate and the inner bay divided into eastern and western sections by the Harpswell Neck peninsula.

In addition to Portland, Cape Elizabeth, and Phippsburg, municipalities with shorelines fronting Casco Bay include Brunswick, Cumberland, Falmouth, Freeport, Harpswell, South Portland, West Bath, Yarmouth, and the island towns of Chebeague Island and Long Island.

Researchers with the U.S. Geological Survey have dated volcanic material embedded in exposed bedrock in Casco Bay to the Ordovician period roughly 470 million years ago, predating the formation of the Atlantic Ocean by some 320 million years. The Norumbega fault developed just inland from the Maine coast, with the geologic fault running roughly parallel to the coastline, including a portion of the northern shore of Casco Bay. The Flying Point fault in Casco Bay is considered part of the Norumbega fault system, dividing bedrock formations that have distinct geological characteristics.

Around 14,000 BCE during the Wisconsin glaciation period at the end of the last glacial cycle, the Laurentide ice sheet covering the Casco Bay region began to recede, according to radiocarbon dating on marine shells and other materials. The glacier's retreat stripped bare underlying bedrock to form the rocky coast of Casco Bay's shore and islands.

According to NOAA's soundings, the bay's deepest point is about 204 feet, southwest of Halfway Rock. A Phippsburg hill called Fuller Mountain has the bay's highest elevation along the immediate shoreline, estimated at 269 feet above sea level by the U.S. Geological Survey in 1980, and 277 feet on more recent topographical maps. Sebascodegan Island has the highest elevation of any Casco Bay island at 201 feet on a hill called Long Reach Mountain, followed by Great Chebeague Island at 176 feet.