Large, exotic (those whose headwaters are in distant places) rivers are some of the most unique and diverse ecosystems on earth. Because they often flow through a multitude of biomes and climates, their waters are a vital resource not only for the organisms that inhabit these rivers, but for human societies as well. Thus, large rivers, like the Rio Grande, that flow through arid and agricultural regions are highly regulated and diverted. Regulation and dewatering upset a river’s natural flow regime (e.g., magnitude, duration, timing of large flood events), subsequently impacting the river’s ability to transport its sediment supply, and eventually perturbing a river into either sediment surplus or deficit. The combination of altered flow and sediment regimes influence the availability of habitat essential for the survival and viability of aquatic organisms, such as fish and invertebrates. In addition, increased deposition of sediment creates areas suitable for invasive riparian vegetation to establish, likely affecting habitat complexity and increasing the abundance of leaf litter deposited into the river. The altered flow and sediment regimes, in combination with invasive riparian vegetation, culminate and eventually affect the food resources and aquatic communities present in a river ecosystem. Most often, the links between the physical perturbations to a system with the biological factors are poorly understood. In this study, we use distinct segments of the Rio Grande along the US-Mexico border to compare areas with greater and lower habitat heterogeneity, water quality, and invasive riparian species abundance to better understand what physical factors can influence aquatic species such as fish and invertebrate communities. We identify critical limiting factors for the native fish community present, and link the altered flow and sediment regimes with the aquatic ecological template of the Rio Grande.