Draining the extreme western part of Pictou County, it flows into Amet Sound on the Northumberland Strait at River John, a village which takes its name from the river.

In the nineteenth century, the river was an important scene of wooden ship building.

In 1884, the largest ship ever built in Pictou County, the 1,687-ton Warrior was launched by the Kitchin yard, while rival Archibald MacKenzie launched the 1,574-ton Caldera that same year.

[5] The upper reaches in the Cobequid Hills began to be settled in the early nineteenth century at West Branch River John, Diamond, Loganville, and Dalhousie Settlement.

According to estimates by the Province of Nova Scotia, in 2011 there were 6,661 people resident within the River John watershed (i.e., all land draining into Amet Sound).