After flowing through Rockhampton, the river flows south by east past the Berserker Range past Humbug Point to the south of the Flat Top Range and eventually discharging into Keppel Bay in the Coral Sea near the MacKenzie Island Conservation Park.

The Fitzroy River catchment system has many weirs and dams, used for farming, mining and domestic consumption.

In the main Fitzroy River sub-catchment the only reservoirs are the Eden Bann Weir and the Fitzroy River Barrage, with the latter capable of holding 61,000 megalitres (1.3×1010 imp gal; 1.6×1010 US gal) when full,[5] to provide potable water to Rockhampton city and surrounds.

The Fairbairn Dam on the Nogoa River and several weirs downstream on the Mackenzie River provide water for irrigating a wide range of crops including cotton, peanuts, chickpea, corn and horticulture including citrus, table grapes, melons, supplying water for coal mines and domestic use for the town of Emerald.

[9] The traditional owners of the area in the Fitzroy River catchment are the Darumbal people, notably the Baiali[10] and Jetimarala clans.

During the 19th and early 20th centuries, the city was a major port, however rocky bars in the river prevented the Fitzroy from being used for navigation any further inland.

[14] Glenmore Homestead was built at a property on the northern bank of the river seven kilometres (4.3 mi) northwest of Rockhampton.

[22] In 2018, the Fitzroy River in Rockhampton was incorporated into the Queen's Baton Relay prior to the 2018 Commonwealth Games.

[5] The prized Australian fish, the barramundi, breeds in the river along with sooty grunter and a separate genetic strain of golden perch.

[25] At the mouth of the river researchers have discovered a genetically distinct snubfin dolphins species with a population of just 70 animals.

The World Wildlife Fund had concerns that a planned coal port on Balaclava Island by Xstrata could wipe out the local snubfin population.