Adults face predation from Spectacled Caimans and small cats. Various raptors and large birds target different life stages: Southern Caracaras, Snail Kites, and Great Black Hawks take adults, while herons, storks, and various hawks and eagles prey on juveniles and hatchlings. The Gold Tegu (a large lizard) preys on both eggs and adults. Nests are also raided by Crab-eating Raccoons and tegus.

The months spent buried during estivation may expose turtles to predators they wouldn't encounter in water, though specific data on this vulnerability is lacking.

Rather than hibernating through winter, this species estivates during the dry season—a crucial adaptation for surviving in a landscape where water bodies can disappear for months. When streams dry up, turtles leave the water and bury themselves under leaf litter, tree roots, or spiny shrubs. They've been found estivating as far as one kilometer from the nearest water and can remain buried for up to 120 days.

To survive this extended dormancy, the turtles retain large amounts of water in their bladders to prevent desiccation. Groups of individuals sometimes estivate close together, though they don't all appear to begin dormancy at the same time—researchers have found thin, empty-stomached turtles alongside well-fed individuals with algae still growing on their shells.

This species is an opportunistic omnivore that feeds primarily at night while in the water. The diet centers on snails (particularly apple snails), crustaceans, crabs, aquatic insects, tadpoles, frogs, small fish, and carrion, with occasional plant material. The large head and powerful jaw muscles appear well-suited for crushing snail shells. Interestingly, researchers have found ants in the stomachs of estivating individuals, suggesting they may also feed on land when the opportunity arises.

Reproductive ecology remains poorly understood in wild populations. Captive observations suggest mating occurs primarily in June and July in shallow water. In Córdoba, egg-laying takes place during the dry months from October to March, with hatchlings emerging between April and May.

Females may nest considerable distances from water—one nest was found about a kilometer from the nearest stream. Clutch size appears variable, with reports ranging from 6 to 12 eggs. Eggs are nearly spherical, measuring roughly 34 x 29 mm and weighing about 16 grams. Under captive conditions, incubation lasts approximately four months with high hatching success (92%). The presence of eggs at various developmental stages in females suggests the species may produce multiple clutches per year.

This turtle holds a unique biogeographic distinction as the only member of the side-necked turtle family Chelidae found northwest of the Andes—all other South American chelids occur east of this mountain range. Genetic studies have revealed a close relationship with Mesoclemmys zuliae from Venezuela, though the two remain distinct species despite their weak genetic divergence.

The species shows remarkable site flexibility, with annual home ranges spanning 9 to 31 hectares. Individuals may use or cross streams, riparian forest, pastures, and isolated pools in open areas. During the transition from rainy to dry season, some turtles make substantial movements—likely searching for suitable estivation sites or more permanent water bodies.