Few studies have contrasted faunal communities between flooded and unflooded tropical forests, and such attempts have largely been restricted to a few taxonomic groups. We present the first comparison of the composition and structure of an entire assemblage of mid-sized to large-bodied mammals in adjacent unflooded (terra firme) and flooded (várzea) forests of central-western Amazonia. We extend this comparison to 13 other terra firme and várzea forest sites in order to examine the fundamental dichotomy between mammal communities in these Amazonian environments. We found a consistently impoverished fauna in várzea environments both in terms of primates and other non-volant mammals, although primate density and biomass was substantially higher in várzea than in terra firme. The average Bray–Curtis mammal community dissimilarity between terra firme and várzea forests was 74%, whereas mean dissimilarity within várzea and terra firme samples was 40% and 39%, respectively. The results seem to be largely a function of high habitat heterogeneity and floristic diversity in terra firme and the physical connectivity and proximity of várzeas to adjacent terra firme forests. We suggest that inundated forests should be set aside as a crucial complement to Amazonian reserves dominated by terra firme forests in future biodiversity conservation planning.