Background: The threats facing Ecuador's Yasuní National Park are emblematic of those confronting the greater western Amazon, one of the world's last high-biodiversity wilderness areas. Notably, the country's second largest untapped oil reserves - called "ITT" - lie beneath an intact, remote section of the park. The conservation significance of Yasuní may weigh heavily in upcoming state-level and international decisions, including whether to develop the oil or invest in alternatives. Methodology/Principal Findings: We conducted the first comprehensive synthesis of biodiversity data for Yasuní. Mapping amphibian, bird, mammal, and plant distributions, we found eastern Ecuador and northern Peru to be the only regions in South America where species richness centers for all four taxonomic groups overlap. This quadruple richness center has only one viable strict protected area (IUCN levels I-IV): Yasuní. The park covers just 14% of the quadruple richness center's area, whereas active or proposed oil concessions cover 79%. Using field inventory data, we compared Yasunís local (alpha) and landscape (gamma) diversity to other sites, in the western Amazon and globally. These analyses further suggest that Yasuní is among the most biodiverse places on Earth, with apparent world richness records for amphibians, reptiles, bats, and trees. Yasuní also protects a considerable number of threatened species and regional endemics. Conclusions/Significance: Yasuní has outstanding global conservation significance due to its extraordinary biodiversity and potential to sustain this biodiversity in the long term because of its 1) large size and wilderness character, 2) intact largevertebrate assemblage, 3) IUCN level-II protection status in a region lacking other strict protected areas, and 4) likelihood of maintaining wet, rainforest conditions while anticipated climate change-induced drought intensifies in the eastern Amazon. However, further oil development in Yasuní jeopardizes its conservation values. These findings form the scientific basis for policy recommendations, including stopping any new oil activities and road construction in Yasuní and creating areas offlimits to large-scale development in adjacent northern Peru.