Cook Inlet stretches 180 miles (290 km) from the Gulf of Alaska to Anchorage in south-central Alaska. Cook Inlet branches into the Knik Arm and Turnagain Arm at its northern end, almost surrounding Anchorage. On its south end merges with Shelikof Strait, Stevenson Entrance, Kennedy Entrance and Chugach Passage.
The watershed covers about 100,000 km² of southern Alaska, east of the Aleutian Range, south and east of the Alaska Range, receiving water from its tributaries the Knik River, the Little Susitna River, and the Susitna and Matanuskarivers. The watershed includes the drainage areas of Denali. Within the watershed there are several national parks and the active volcano Mount Redoubt, along with three other historically active volcanoes. Cook Inlet provides navigable access to the port of Anchorage at the northern end, and to the smaller Homer port further south.