We employ the approach of Roderick and Farquhar (2011) to assess the sensitivity of runoff (R) given changes in precipitation (P), potential evapotranspiration (Ep ), and other properties that change the partitioning of P (n) by estimating coefficients that predict the weight of each variable in the relative change of R. We use this framework using different data sources and products for P, actual evapotranspiration (E), and Ep within the Amazon River basin to quantify the uncertainty of the hydrologic response at the subcatchment scale. We show that when estimating results from the different combinations of datasets for the entire river basin (at Óbidos), a 10% increase in P would increase R on average 16%, while a 10% increase in Ep would decrease R about 6%. In addition, a 10% change in the parameter n would affect the hydrological response of the entire basin around 5%. However, results change from catchment to catchment and are dependent on the combination of datasets. Finally, results suggest that enhanced estimates of E and Ep are needed to improve our understanding of the future scenarios of hydrological sensitivity with implications for the quantification of climate change impacts at the regional (subcatchment and subbasin) scale in Amazonia.