It begins at the western end of the Porcupine Hills at Piwei Lakes and heads in an easterly direction through a glacier-formed valley and into the Etomami River, which is a tributary of the Red Deer River.

Save for a small recreation park on the river's north bank, there are no communities nor settlements along its course.

[5][6] Piwei River begins south of the town of Porcupine Plain at an elevation of 511 m (1,677 ft) in a chain of several lakes called the Piwei Lakes[7] at the western end of the Porcupine Hills.

From the lakes, it heads east through the Porcupine Provincial Forest and glacier-formed valleys en route to its terminus at the Etomami River.

It is about 8 ha (20 acres) in size and 509 metres (1,670 ft) above sea level.