The river rises from the eastern slopes of the Blackall Range and flows east-northeast, similar to the Maroochy River to the north.

Mountain Creek is another tributary that rises on the Buderim mountain that divides the Mooloolah and Maroochy watersheds.

Although the Mooloolah River doesn't experience major flooding often, a flood warning system was established in 2004 to inform the Sunshine Coast Regional Council with river height predictions from network of rainfall and river height field stations.

Captain James Cook, on board the HM Bark Endeavour, sighted the Mooloolah River during his northward voyage along the Queensland coast in 1770.

In 1960, the Mooloolah River was adjoined to the Mooloolah River National Park to protect valuable remnants of coastal habitats.