The St. Joseph River drainage basin covers 4,685 square miles (12,130 km2), and is the third largest watershed draining to Lake Michigan.

Historically, the river served as an important canoe transportation route for various Native American tribes, and for French Canadian Voyageurs.

The watershed includes 3,742 river miles (6,022 km) and flows through and near the Kalamazoo-Portage, Elkhart-Goshen, Mishawaka-South Bend, and St. Joseph/Benton Harbor metropolitan areas.

In northern Indiana, the river flows west-southwest through Elkhart, Mishawaka, and South Bend, where it turns abruptly to north to re-enter southwestern Michigan in southeastern Berrien County.

[7] saakiiweesiipiiwi (Outlet River, also historically spelt Sakiwasipi),[8] as it was called by the Miami people, was inhabited for thousands of years by various indigenous tribes as it served an essential trade avenue in the Great Lakes region.

On November 1, 1679 René Robert Cavelier, Sieur de La Salle sailed southeast across Lake Michigan and built Fort Miami at the mouth of the river.

After giving up on the return of his ship, Le Griffon, in April 1680, he became the first European to walk the well traveled indigenous routes east across the Lower Peninsula of Michigan back to the Detroit River and Canada.

European American settlement of the St. Joseph river basin area began to increase in earnest after southwestern Michigan was surveyed in 1829.

[11] From the early 1830s until 1846, the river bore various commodities from upstream to a busy port at St. Joseph, where they were loaded onto lake boats for shipment to Chicago and elsewhere.

[9] On April 11, 1893, a Lake Michigan seiche (a phenomenon similar to an ocean tsunami) pushed a wall of water, 3 to 5 feet (0.91 to 1.52 m) high, up the river at St. Joseph and Benton Harbor.

[13] The water rights to what would become the East and West Races were claimed by Alexis Coquillard and Lathrop Taylor in 1831, when the city of South Bend was founded.

[13] In 1973 the Oliver Chilled Plow Works hydro-electric plant was demolished to make room for construction of the Century Center, which was completed in 1977.

[18] Through the use of movable barriers and obstacles, the East Race can be configured to provide a whitewater course for recreational and competitive canoeing, kayaking and rafting.

Rare plants include prairie dropseed (Sporobolus heterolepis), rosinweed, tall beak rush, and umbrella grass.

The wetlands and floodplain forests provide habitat to nearly half of all migratory birds in Indiana and Michigan and are a vital habitat for resident species as well, such as wild turkey (Meleagris gallopavo), coyote (Canis latrans), fox, beaver (Castor canadensis), mink (Neogale vison), Indiana bat (Myotis sodalis), eastern box turtle (Terrapene carolina carolina), and the rare spotted turtle (Clemmys guttata) and northern redbelly snake (Storeria occipitomaculata occipitomaculata), both protected by the state of Michigan.

In 1980 the Michigan Department of Natural Resources, Indiana Department of Natural Resources and United States Fish and Wildlife Service signed the "St. Joseph River Interstate Cooperative Salmonid Management Plan", which led to construction of fish ladders at the Buchanan, Niles, South Bend and Mishawaka dams.

Historically, the migrating native species included lake sturgeon (Acipenser fulvescens), bass (smallmouth and largemouth), redhorse (silver, golden, shorthead, river, and greater) (Moxostoma ssp.

In 2002 FotSJR developed the St. Joseph River Watershed Management Plan, with grant support from the Michigan Department of Environmental Quality.

The river delivers significant pollutants to Lake Michigan - including sewage overflows from riverside communities, sediments and toxic substances such as mercury and polychlorinated biphenyl (PCB).