The river is located in the northwestern Lower Peninsula of the state, flowing into Lake Michigan at Frankfort.

A corruption of this pronunciation led to the name of Benzie County.

Although not considered part of the Betsie River today, older maps of the area do say so.

A dam on the river forms Homestead Pond, after which is flows mostly west and slightly north to Lake Michigan.

The Betsie River drains an area of approximately 155,026 acres (627.37 km2)[5] in three counties.