: Human settlements have historically thrived near rivers for navigation, trade, and availability of water supply and resources. Night light data, representing economic activities provide a novel approach to studying the interactions between human activity and rivers over time. Here, we use the Defense Meteorological Satellite Program (DMSP) stable night light data from 2000-2013 as a proxy for human presence and activities to quantify the statistical relationships between night light presence and intensity in the Indus Basin, Asia. We test how these data are affected by proximity to trunk channels and by channel type (single/multi-thread) in the study area. We find that night light presence is enhanced by 26% within a 0 to 5 km proximity range of the Indus River and its tribu-taries, relative to the basin as a whole. We interpret this to represent increased human presence and activity within this zone. However, the mean intensity is lower near the river and higher away from the river signifying denser settlements, such as towns and cities which are preferentially located away from the Indus and its tributaries. Moreover, the enhancement of lit pixels signifying human presence and activities is increased by 18% near single-thread sections of the Indus River, compared to segments of the Indus displaying multi-thread morphologies. We suggest that this is due to the enhanced stability of single-threaded channels, relative to mobile multi-threaded channel reaches. This study demonstrates how night lights are an important tool to constrain the relationship between human presence and river dynamics in large catchments such as the Indus, and we suggest this data will have an important role in assessing differential flood spatial and social vulnerability at a regional scale.