Located in Gladwin and Midland counties, the river rises in Beaverton at the confluence of the river's North, Middle, and South branches in Ross Lake.

On older maps, the South branch and the lower course of the Tobacco River are identified as Samaquasebing, Assemoqua, Assymoquoasibee, etc., all derived from the Ojibwe Asemaakwe-ziibi(ing), meaning "(At) Tobacco-woman River".

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