In September 2002, an article in National Geographic raised concerns about a controversial deal made with Nestlé Waters North America, giving them permission "to bottle up to 210 million gallons (about 800 million liters) a year from an aquifer north of Grand Rapids, Michigan that recharges the Muskegon River".

The watershed flows through the cities of Muskegon, Newaygo, Big Rapids, Evart, and Houghton Lake.

Winfield Scott Gerrish established a seven-mile-long logging railroad from Lake George to the Muskegon River.

[5] There is abundant wildlife, including black bear, otters, waterfowl, white-tailed deer, and bald eagles and, despite increasing development, some areas are still fairly remote and natural with much of the surrounding land composed of state-owned tracts.

The majority of the bicycle and pedestrian trail crossings are former railroad bridges which have been converted to non-motorized traffic.The three major dams of the Muskegon River (Rogers, Hardy and Croton) generate about 45,600 kilowatts, with about 30,000 of that from Hardy Dam.