The Whetstone is formed by the confluence of its North and South forks 4 miles (6 km) northeast of Milbank, South Dakota and flows generally eastward across the Coteau des Prairies in northern Grant County, past Big Stone City.

At Big Stone City, the river has a mean annual discharge of 69 cubic feet per second.

The North Fork flows southeastward from Roberts County and passes near the town of Wilmot.

The South Fork flows westward in Grant County and passes the town of Milbank.

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