Nest-site selection exerts a fundamental maternal effect on offspring fitness in oviparous species. In many freshwater turtles, females do not care for their eggs after oviposition but rather rely on a nest’s micro-environment to incubate developing embryos although linkages between oviposition choices and overall fitness remain poorly evaluated. We tested predictions derived from multiple hypotheses to examine nesting patterns of the yellow-spotted river turtle Podocnemis unifilis, a species imperiled by egg harvesting by humans throughout its range, based on data collected from 73 nesting sites along 118 km of river in the eastern Brazilian Amazon. Nesting area size largely explained nest-site selection by turtles, but only weakly explained turtle egg harvesting by humans. Despite the wide availability of alternative nesting habitats, turtles do not appear to be capable of avoiding hazardous nesting sites associated with increased egg harvesting by humans. Because signals used by female turtles to select nesting areas are apparently not sufficient for avoiding nesting along rivers accessible to humans, direct conservation action will be vital for persistence of these and likely other Amazonian freshwater turtles.