Distribution patterns reflect the interactions of organisms with their environment. We discuss the distribution patterns of Nile Crocodiles (Crocodylus niloticus) in a naturally patchy floodplain environment with the use of aerial survey data collected over the last 40 yr. Although only 10,000 ha in size, Ndumo Game Reserve (NGR) supports one of the largest wild crocodile populations in South Africa, largely because of landscape complementation with neighboring Mozambique. Distributions within the NGR were influenced by landscape physiognomy and composition as well as connectivity and corridor quality. To quantify the effects of environmental conditions on crocodile distribution, we conducted 40 diurnal counts at Lake Nyamithi in the NGR between 2009 and 2012. Average monthly maximum temperature had an effect on the number of crocodiles in Lake Nyamithi; however, environmental variables influenced different size classes of Nile Crocodiles to a varying extent. Anthropogenic disturbances influenced the functionality of the floodplain landscape negatively, with impacts on habitat use and connectivity. It is considered essential that a cross-border conservation program be initiated in order to conserve the current population of Nile Crocodiles in the greater NGR area.