Grand Canyon is the most widely recognized large, deep canyon (LDC) on Earth, but while the ecology of the highly regulated Colorado River corridor has been intensively studied, the overall ecology and biogeographic relationship of Grand Canyon to southwestern North America are poorly known. In this presentation I provide an overview of the multitude of ecosystems that comprise the Grand Canyon ecoregion (GCE) in northern Arizona and southern Utah. I begin with an overview of geographic and elevation relationships of this LCD within the Colorado River basin. Like many LDCs, Grand Canyon is a light-limited system, receiving only 70% of the ambient photosynthetically active radiation (PAR) available to ecosystems that are not shaded by cliffs. PAR restriction exerts strong distributional impacts on GCE flora through both direct and indirect (e.g., microclimate) processes, factors that also may have geomorphological consequences. An array of arid grasslands, shrublands, forests, and alpine habitats exist at progressively higher elevations in the GCE, most of which have changed dramatically in post-Pleistocene time, as well as many cave, springs, wetland, and riparian habitats. Among them, most prominent is the Colorado River, which has been intensively regulated by the two largest dams in the contiguous United States - upstream by Glen Canyon Dam (Lake Powell) and downstream by Hoover Dam (Lake Mead). In this, the sesquicentennial of John Wesley Powell’s exploration of the Colorado River, I summarize pre- versus post-dam changes in the ecology of the Colorado River ecosystem (CRE) in Grand Canyon. A largely unrecognized but substantial number of endemic taxa occur in the GCE and CRE. These species typically are restricted to isolated, long-term stable refugial habitats, including caves and springs, severe south-facing slopes at middle elevations, and mountain peaks. The development of biotic assemblages in Grand Canyon, and the evolution of endemism have been constrained by late Neogene climate changes. Despite the highly protected status of Grand Canyon as one of the world’s premier landscape parks, major ecosystems like the CRE and a substantial number of plant and animal species have been eliminated or are at risk of extirpation there. These habitat and biodiversity losses merit consideration in regional conservation and the future protection of this world-renown landscape.