The river's headwaters are in the Coast Range at about 5,000 feet (1,500 m) and it flows roughly northwest until it empties into the Pacific Ocean near the small town of Orick, the only development in the 280-square-mile (730 km2)-watershed.

It flows north through a deep forested valley, receiving many small tributaries including Minor and Lacks creeks from the right.

It then receives Bridge Creek from the left, before winding through several groves of Sequoia sempervirens, more commonly known as redwood trees, from which the stream takes its name.

[5] The long, narrow Redwood Creek drainage basin encompasses 280 square miles (730 km2) on the western slopes of the California Coast Ranges, entirely within Humboldt County.

Elevations range from over 5,000 feet (1,500 m) on higher peaks of the mountains near the headwaters to sea level at the creek's mouth at the Pacific.

In addition, it has destroyed the riparian vegetation, which helps protect against erosion and decreases the water temperature to a level suitable for the creek's coldwater fish.