Combined with its tributary, the South Fork Powder River, it is 550 miles long.

It drains an area historically known as the Powder River Country on the high plains east of the Bighorn Mountains.

The North and Middle forks rise along the eastern slope of the Bighorn Mountains.

The South Fork rises on the southern slopes of the Bighorn Mountains west of Casper.

The combined stream flows northward, east of the Bighorns, and into Montana.