Documentation of the interacting effects of river regulation and climate on riparian vegetation has typically been limited to small segments of rivers or focused on individual plant species. We examine spatiotemporal variability in riparian vegetation for the Colorado River in Grand Canyon relative to river regulation and climate, over the five decades since completion of the upstream Glen Canyon Dam in 1963. Long-term changes along this highly modified, large segment of the river provide insights for management of similar riparian ecosystems around the world. We analyze vegetation extent based on maps and imagery from eight dates between 1965 and 2009, coupled with the instantaneous hydrograph for the entire period. Analysis confirms a net increase in vegetated area since completion of the dam. Magnitude and timing of such vegetation changes are river stage-dependent. Vegetation expansion is coincident with inundation frequency changes and is unlikely to occur for time periods when inundation frequency exceeds approximately 5%. Vegetation expansion at lower zones of the riparian area is greater during the periods with lower peak and higher base flows, while vegetation at higher zones couples with precipitation patterns and decreases during drought. Short pulses of high flow, such as the controlled floods of the Colorado River in 1996, 2004, and 2008, do not keep vegetation from expanding onto bare sand habitat. Management intended to promote resilience of riparian vegetation must contend with communities that are sensitive to the interacting effects of altered flood regimes and water availability from river and precipitation.