It originates from the junction of the Limay River and Neuquén River at the border with the Neuquén Province, and flows southeast to the Atlantic Ocean at , near El Cóndor beach resort some 30 kilometres (19 mi) downstream from Viedma, Río Negro province's capital.
The river served as natural demarcation between "civilisation" and the aboriginal territories during the Conquest of the Desert of late 19th century.
The river crosses the steppe plains of the province through a forest of around 3 kilometres (1.9 mi) in the Alto Valle, and as wide as 20 kilometres (12 mi) towards the Valle Inferior. In the dry plain it is possible to find seashells and pebble.
The main cities in Alto Valle are: General Roca, Cipolletti, Cinco Saltos, followed by many others on the National Route #22. Together with San Carlos de Bariloche, this is the most prosperous part of the province. Most pear and apple plantations are at the Alto Valle, but many also at the Valle Medio.
Besides apple and pear cultivation, tomato is also an important crop, being Lamarque the National Capital of the Tomato. Outside the valley, on the more arid lands around town such as Chimpay and Darwin, some cattle is also raised.
Although the term is not as used term as the previous two, Valle Inferior refers to Viedma and all the cities on the province's coast. Fruit is also produced but is not a primary activity. Onion is cultivated as well as some cereals. Alfalfa and maize is cultivated both for human consumption and for feeding cattle, which is the most important activity.
In spite of its name of Negro ("black") the colour is more greenish than black. Nevertheless, the name is the literal translation of its aboriginal Mapuche name of Curú Leuvú. The river was also known by the name of Río de los Sauces ("River of Willows") for the abundant weeping willows along his lower course.