The conservation status of large-bodied mammals is dire. Their decline has serious consequences because they have unique ecological roles not replicated by smaller-bodied animals. Here, we use the fossil record of the megafauna extinction at the terminal Pleistocene to explore the consequences of past biodiversity loss. We characterize the isotopic and body-size niche of a mammal community in Texas before and after the event to assess the influence on the ecology and ecological interactions of surviving species (>1 kg). Preextinction, a variety of C4 grazers, C3 browsers, and mixed feeders existed, similar to modern African savannas, with likely specialization among the two sabertooth species for juvenile grazers. Postextinction, body size and isotopic niche space were lost, and the δ13C and δ15N values of some survivors shifted. We see mesocarnivore release within the Felidae: the jaguar, now an apex carnivore, moved into the specialized isotopic niche previously occupied by extinct cats. Puma, previously absent, became common and lynx shifted toward consuming more C4-based resources. Lagomorphs were the only herbivores to shift toward C4 resources. Body size changes from the Pleistocene to Holocene were species-specific, with some animals (deer, hare) becoming significantly larger and others smaller (bison, rabbits) or exhibiting no change to climate shifts or biodiversity loss. Overall, the Holocene body-size-isotopic niche was drastically reduced and considerable ecological complexity lost. We conclude biodiversity loss led to reorganization of survivors and many "missing pieces" within our community; without intervention, the loss of Earth's remaining ecosystems that support megafauna will likely suffer the same fate.