The Manitowoc River originates in eastern Wisconsin and flows generally eastward for approximately 40 miles before emptying into Lake Michigan at the city of Manitowoc. The river's watershed covers about 526 square miles, draining portions of Manitowoc, Calumet, and Brown counties. Its main tributary is the North Branch, which joins the mainstem near Clarks Mills. The river has two distinct sections. The upper half above Clarks Mills is wide, sluggish, and marshy with a soft bottom and minimal gradient. Below Clarks Mills, the river's character changes dramatically as it descends through the Niagara Escarpment, featuring a series of rapids and small waterfalls that make it popular for paddling.

For paddlers, the most appealing stretch runs from Clarks Mills to Lake Michigan, offering about 25 miles of navigable water. The 10-mile section from Clarks Mills to County Highway S is particularly scenic, with continuous Class I-II rapids. Below Highway S, the river alternates between swift currents and slower pools as it approaches the city of Manitowoc. The river's difficulty ranges from Class I to II+, making it suitable for intermediate paddlers with some whitewater experience. However, high water levels can increase the challenge, especially at features like Lower Cato Falls. The best paddling is typically from late spring through early fall when water levels are moderate.

Wildlife along the river includes deer, muskrats, and a variety of waterfowl. The corridor supports diverse plant communities, from floodplain forests to prairie remnants.

Key landmarks include the historic Mill Street Dam, the scenic Lower Cato Falls, and several bridges that serve as convenient put-in and take-out points. The river passes through small towns like Clarks Mills and Cato before entering the more urban environment of Manitowoc. Popular access points include Clarks Mills, County Highway S, North Union Road, and the Manitowoc River Access Park. These are all within a 30-minute drive of the city of Manitowoc.

Historically, the river played a crucial role in the region's logging and shipbuilding industries. Today, it's an important recreational resource and the focus of local conservation efforts.

Paddlers should be aware of potential strainers, especially in high water, and the presence of the Mill Street Dam, which requires a portage. Local regulations require life jackets, and paddlers should check water levels before embarking. While most trips are day paddles, multi-day adventures are possible by camping at designated sites along the river or in nearby state parks.