Quantifying the impact of land use and cover (LUC) change on catchment hydrological response is essential for land-use planning and management. Yet hydrologists are often not able to present consistent and reliable evidence to support such decision-making. The issue tends to be twofold: a scarcity of relevant observations, and the difficulty of regionalizing any existing observations. This study explores the potential of a paired catchment monitoring network to provide statistically robust, regionalized predictions of LUC change impact in an environment of high hydrological variability. We test the importance of LUC variables to explain hydrological responses and to improve regionalized predictions using 24 catchments distributed along the Tropical Andes. For this, we calculate first 50 physical catchment properties, and then select a subset based on correlation analysis. The reduced set is subsequently used to regionalize a selection of hydrological indices using multiple linear regression. Contrary to earlier studies, we find that incorporating LUC variables in the regional model structures increases significantly regression performance and predictive capacity for 66% of the indices. For the runoff ratio, baseflow index, and slope of the flow duration curve, the mean absolute error reduces by 53% and the variance of the residuals by 79%, on average. We attribute the explanatory capacity of LUC in the regional model to the pairwise monitoring setup, which increases the contrast of the land-use signal in the data set. As such, it may be a useful strategy to optimize data collection to support watershed management practices and improve decision-making in data-scarce regions.