The Monongahela River is formed at Fairmont by the merging of the West Fork and Tygart Valley River. The "Mon," as it is often called by people of the region, terminates 128 miles away at Pittsburgh, where it joins the larger Allegheny to form the Ohio River. Navigable for its entire length due to a system of locks and dams, the river drains a basin of 7,340 square miles. An ancient predecessor river was once blocked by glacier ice north of Pittsburgh to form the prehistoric Lake Monongahela, which occupied portions of present Ohio, Pennsylvania, and West Virginia.

The Monongahela watershed includes much of north-central West Virginia, southwestern Pennsylvania, and western Maryland. The Cheat River joins the Monongahela in Pennsylvania just north of Morgantown, and another major tributary, the Youghiogheny River, enters near Pittsburgh. Fairmont and Morgantown are the major cities on the Monongahela, apart from Pittsburgh at the river's mouth.

Early downstream commerce was by flatboats built at Morgantown and other points along the river. Too heavy and cumbersome to travel back upstream, they were floated downstream and sold for lumber at the end of the journey. Later, keelboats operated in both directions. These graceful craft, with a central keel from which ribs curved upward to create a cargo box, had a narrow deck on each side along which men walked, pushing poles against the river's bottom and banks.

One of the early and very famous products of commerce transported on the river was Monongahela rye, a whiskey sold and respected as far downstream as New Orleans. On March 3, 1791, Congress placed a tax on distilled spirits. This enraged the makers, and the short-lived Whiskey Rebellion of 1794 resulted.

On March 17, 1811, the first steamboat on a western river, the New Orleans, was launched on the Monongahela at Pittsburgh. It wasn't until April 1826 that a steamboat traveled as far upstream as Morgantown. In 1837, the Monongahela Navigation Company was formed to improve the river for navigation. By 1844, four dams had been built upstream from Pittsburgh. Two additional dams were built in 1854 and 1865. In 1871, the federal government conducted a survey of the river and as a result eventually built another nine dams, finishing with No. 15 in 1904. This made the Monongahela the first river in the United States to be totally controlled for navigation. The modern system of nine locks and dams was built 1904—64, with six dams in Pennsylvania and three in West Virginia. As late as 1930, a major drought lowered the Mon's water level so much that it was possible in places to walk across the river bottom.

Despite the navigation dams, the lower Monongahela flooded heavily in 1907, causing more than $100 million of damage along the river and in the city of Pittsburgh. An aroused public supposedly pointed to the timbered and burned-over watersheds of the Monongahela tributaries—the Cheat, Buckhannon, West Fork, and Tygart Valley rivers—as the cause. Congress passed the Weeks Law in 1911, providing for the establishment of national forests as a way of reforesting lands to prevent subsequent floods. West Virginia was one of the first two southern states to pass enabling legislation, and the first steps to establish the Monongahela National Forest were taken in 1915.