The Cowlitz has a 2,586-square-mile drainage basin, located between the Cascade Range in eastern Lewis County, Washington and the cities of Kelso and Longview. The river is roughly 105 miles (169 km) long, not counting tributaries.

Major tributaries of the Cowlitz River include the Cispus River and the Toutle River. The Cowlitz River currently has 3 major hydroelectric dams, with several small-scale hydropower and sediment retention structures within the Cowlitz Basin.

Where Highway 12 crosses Mayfield Lake, just west of Mossyrock, causeways were built out to the middle of the lake, where a short bridge section connects the two sides. A small bridge provides a crossing for SR 122 at the head of Mayfield Lake. Just east of Mossyrock, the Cowlitz River Bridge on Highway 12 was the largest concrete arch bridge in North America until 1971 at 550 feet (170 m).

At the head of Riffe Lake, the 27 Road provides access to the forestland south of the Cowlitz from Morton and Glenoma to the north.

At Randle, SR 131 crosses the Cowlitz to provide access to the Cispus basin and the northern areas of the Mount St. Helens National Volcanic Monument.

Between Randle and Packwood, Highway 12 crosses the Cowlitz at the Cora bridge.

At Packwood, Skate Creek Road spans the river, providing access to the Gifford Pinchot National Forest and Tatoosh Wilderness, as well as connecting the downtown and residential areas of Packwood.

Upstream from Packwood, the Cowlitz splits into the Muddy and Clear Forks, with several Forest Service and Park Service roads crossing each.