This study examines the impact of an elaborated irrigation system on the natural resources and society in the deltaic part of the Indus River in Pakistan. Time series information was collected to analyze the ecological and natural resource dynamics, and their impacts on the structure and quality of the occupations of the people in the Indus delta during pre- and post-irrigation system development periods. The information was collected through literature review, reconnaissance, structured questionnaire survey, focus group discussions, and interviews. The findings revealed that the expansion of the irrigation system and the resulting reduction in the downstream flow had their differential impacts on the various segments of downstream ecology and society. Some of the resources, for example the agricultural mudflats have been adversely affected due to the accelerated seawater intrusion that severely impinged on the paddy farms. On the other natural resources like mangroves, the impacts had been both negative and positive. On one hand, the diversity of the mangroves species had deteriorated while on other hand, the mangroves have benefited from such development because of the alleviated pressure of camel grazing as a result of the occupational change on the part of the camel herders. Furthermore, changes in the hydrological regimes had forced the paddy farmers and camel herders to switch to fishing as an alternative source of employment and income. Considering that currently about 87% people are already engaged primarily in marine fishery, this scenario is threatening the sustainability of the fishery resources as well as the livelihoods of all, the traditional and converted fishermen. The findings of the study are therefore meant to advocate the different treatments which should be accorded to the various segments of the downstream ecology and society during the planning of any remedial irrigation projects in order to mitigate the adverse impacts of the previous irrigation development strategies and of any water resources development to be carried out in the future.