[1] It has a watershed area of 1,409 square kilometres (544 sq mi)[2] The name "Musquodoboit" is Mi'kmaq, roughly translated to "beautiful water".

Rising in the Cobequid Mountains, the river runs in a southwesterly direction along the Halifax-Colchester county line through the fertile Musquodoboit Valley; Glenmore Mountain is on the north and a series of low hills are on the south.

Near the halfway point, the river changes course at a right angle, running toward the southeast where it empties into a bay on the Atlantic Ocean called Musquodoboit Harbour.

The river is a popular recreational destination in central Nova Scotia, as its calm and lack of rapids or waterfalls makes it ideal for paddling sports like canoeing and kayaking.

According to estimates by the Province of Nova Scotia, there were 27,846 people residing within the Musquodoboit River watershed in 2011.