The headwaters of the river rise near Belmunging then flow in a northerly direction, crossed by the Goldfields Road and continuing in a north-westerly direction to finally flow parallel to the Northam York Road and crossed by the Great Eastern Highway. There river is joined by three minor tributaries; Mortlock River North, Mortlock River East and Meenaar South Creek. The river discharges into the Avon River, just west of Northam. The Mortlock descends 103 metres (338 ft) over its 81-kilometre (50 mi) course.
The river was named after the surveyor Henry Mortlock Ommanney in the 1830s. Ommanney was the first European to discover the river during an expedition through the area in 1835.
The river is saline and delivers the most salt (approximately 91 tonnes (90 long tons) per year) into the Avon River.