Flood monitoring was conducted using multi-sensor data from space-borne optical, and microwave sensors; with cross-validation by ground-based rain gauges and streamflow stations along the Indus River; Pakistan. First; the optical imagery from the Moderate Resolution Imaging Spectroradiometer (MODIS) was processed to delineate the extent of the 2010 flood along Indus River; Pakistan. Moreover; the all-weather all-time capability of higher resolution imagery from the Advanced Synthetic Aperture Radar (ASAR) is used to monitor flooding in the lower Indus river basin. Then a proxy for river discharge from the Advanced Microwave Scanning Radiometer (AMSR-E) aboard NASA’s Aqua satellite and rainfall estimates from the Tropical Rainfall Measuring Mission (TRMM) are used to study streamflow time series and precipitation patterns. The AMSR-E detected water surface signal was cross-validated with ground-based river discharge observations at multiple streamflow stations along the main Indus River. A high correlation was found; as indicated by a Pearson correlation coefficient of above 0.8 for the discharge gauge stations located in the southwest of Indus River basin. It is concluded that remote-sensing data integrated from multispectral and microwave sensors could be used to supplement stream gauges in sparsely gauged large basins to monitor and detect floods.