Just after it crosses the state boundary into Three Oaks Township in Berrien County, Michigan, it is joined from the east by Spring Creek to form the South Branch Galien River.

In comparison to other watersheds along the Lake Michigan coastal area, the Galena River has not been significantly impacted by human influence,[6] Within Indiana, the Galena River watershed is located within the physiographic unit known as the Valparaiso Morainal Area.

The Galena River originates from two wetland sources, the 165-acre (67 ha) Galena Wetland Conservation Area and a 45-acre (18 ha) prairie fen called the Springfield Fen Nature Preserve, which join to form the river.

[6] The most common sources of E. coli are livestock operations, failing septic systems, illicit sewage connections, and combined sewer overflows.

The Indiana Department of Natural Resources has designated the Galena River as a salmonid stream, which requires a higher level of water quality standards.