The main river then flows east, north of the Moresby Range National Park, and empties into the Coral Sea.

This branch is the longest and its catchment is drawn from the Malanda Falls Conservation Park, and the following national parks: Ella Bay, Eubenangee Swamp, Herberton Range, Japoon, Malaan, Palmerston Rocks, Topaz Road, Tully Falls, Tully Gorge and Wooroonooran.

[5] The river is subject to periodic flooding[7] (On the 8th of March 2018 the Johnstone burst its banks cutting off Innisfail from Cairns) popular for white-water rafting, and other tourist activities.

[10] The area was first identified by colonial Europeans in 1872 by Captain John Morseby during the search for survivors of the shipwreck Maria, when he named the river the Gladys .

[12] In 1881 the first sugar cane plantation and mill were established at Innisfail after G. E. Dalrymple reported suitable land on the Johnstone River.