This dataset describes the quantity and morphology of microplastics in water, surficial sediment, sediment core, fish, and shellfish samples from Lake Mead National Recreation Area (Nevada/Arizona). Water and surficial sediment samples were collected once at 9 locations. A sediment core (33 cm long) was extracted from Las Vegas Bay to assess changes in microplastic deposition over time. Striped bass (Morone saxatilis), common carp (Cyprinus carpio), quagga mussels (Dreissena bugensis), and Asian clams (Corbicula fluminea) were sampled at a subset of locations to assess biological uptake of microplastics. Sampling and analysis methods are described in the Processing Steps section of the metadata. All samples were collected in March 2017 except the sediment core, which was collected in March 2018.