Animal and plant life is abundant and extremely varied in the reserve. There are over 132 species of mammals, 13 of which are primates. The reserve's waters are home to gray and pink dolphins, Amazonian manatees, Giant river Otters, Black Caimans and giant South American River Turtles. Land species include Jaguars, Capuchin Monkeys and Spider Monkeys. The Black Spider Monkey, the Orange-chested Spider Monkey, the Woolly Monkey, and the Howler Monkey are all considered endangered.

More than 300 species of birds live in Pacaya-Samiria, including five of the eight species of Macaw found in Peru. The prehistoric-looking hoatzin bird is seen here as well.

Wildlife and local villagers rely heavily on two species of palm for food. The fruit of the Moriche Palm is critical to the diets of parrots and mammals such as the Tapir. Humans use the fruit in drinks and ice cream. Birds and mammals feed on the fruit of the Chonta Palm, while humans harvest the palm's heart. No other protected area in Peru is as directly linked to the economic well-being of such a large human population. At least 100,000 "ribereños", or river people, living in and around this part of the Amazonian rain forest rely on its aquatic and terrestrial resources for food and income. Another 600,000 Peruvians live nearby.

The native San Juan de YanaYacu Indians protect 200+ acres of private land on the YanaYacu River, near the confluence of the Maranon, Ucayali, and Amazon rivers. Here the Amazon Refuge wildlife center provides excellent access for a visit to the Pacaya-Samiria National Reserve.