This study aims to assess an area of about 70 km along Indus River in Layyah and Muzaffargarh districts of Punjab, Pakistan, which is highly vulnerable to erosion. Actual erosion and deposition has been quantified for each of left and right bank of river over a period of 2002 to 2016. Open source data product of Landsat was used to identify the spatio-temporal changes of Indus River. A model has been developed that extracted the water from satellite images using NDWI. River path of Indus has been mapped for 2002, 2009 and 2016 during high and low flow seasons which not only signifies the channel shifting and river morphology, but also highlights the zones where water over run into land. It has been observed from the study that river is shifting more towards its left bank and the area is highly vulnerable to erosion. In 2009, river eroded 24.3 km 2 from right bank while it eroded 100 km 2 from left bank. Similarly, in 2016, an erosion of 12.5 km 2 and 71.9 km 2 from right and left bank, respectively, was occurred. The river inundation eroded the major agricultural land and affected the life of people and infrastructure. Results provided the latest and reliable information on the dynamics of Indus River in the study area which can be utilized to develop erosion control program and taking practical measures to ensure the safety of life and infrastructure.