The river has its headwaters to the northwest of Norsewood in the Ruahine Ranges of southern Hawke's Bay. It flows initially eastward before turning south-west near Ormondville, flowing 40 km before turning north-west near Woodville. At this point the river enters the Manawatu Gorge. Beyond the gorge it again turns south-west, flowing through the city of Palmerston North before entering the Tasman Sea at Foxton Beach.
The river is unique among New Zealand rivers, starting on the east side of the main dividing range and having its outflow to the west. The explanation for this is the uplift of the central ranges. The ranges moved upwards at the same time as the gorge was eroded by the river, instead of the more usual erosion of an already existing range. This suggests that the river is an old one, as it must have existed before the Ruahine and Tararua Ranges.
Major tributaries of the river include the Makakahi, Mangahao, Pohangina and Oroua Rivers. The Manawatu's total length is 180 km, making it only the 12th-longest in the country, but at 102 m³/s it is one of the country's greatest rivers in terms of flow, and second only to the Waikato River among North Island rivers.
The river's name comes from the Māori words manawa (heart, spirit) and tū (stand still, or depressed), therefore heart standing still with fear, or depressed spirit (Reed, 1996:47). Haunui was in pursuit of his wife and arrived at this river clutching his chest when he named this river.(Reed, 1996)
The Manawatu River flooded in February 2004, displacing over 2000 people (primarily from Marton and Feilding) and damaging over 1000 Manawatu farms. The cost of the flood in terms of insurance payouts was NZ$122 million. Further damage was prevented by the opening of the Moutoa floodgates, which intercept the river near Opiki.