It rises about 110 km (68 mi) north of Lake Titicaca, in the Arequipa region of Peru and becomes the Amazon at the confluence of the Marañón close to Nauta city.

The Ucayali's width varies from 400–1,200 metres (1,300–3,900 ft), due to the large number of islands.

There are five difficult passes, due to the accumulation of trees and rafts of timber.

The Ucayali is home to the Amazon river dolphin, giant otter, and the Amazonian manatee, which are abundant in Pacaya-Samiria National Reserve, close to Nauta.

The southeastern border of the reserve is formed by the lower Ucayali River.