Forest fire is a common concern in Mediterranean watersheds. Fire-induced canopy mortality may cause the degradation of chemical–physical properties in the soil and influence hydrological processes within and across watersheds. However, the prediction of the pedological and hydrological effect of forest fires with heterogenous severities across entire watersheds remains a difficult task. A large forest fire occurred in 2017 in northern Italy providing the opportunity to test an integrated approach that exploits remote and in-situ data for assessing the impact of forest fires on the hydrological response of semi-natural watersheds. The approach is based on a combination of remotely-sensed information on burned areas and in-situ measurements of soil infiltration in burned areas. Such collected data were used to adapt a rainfall–runoff model over an experimental watershed to produce a comparative evaluation of flood peak and volume of runoff in pre- and post-fire conditions. The model is based on a semi-distributed approach that exploits the Soil Conservation Service Curve Number (SCS-CN) and lag-time methods for the estimation of hydrological losses and runoff propagation, respectively, across the watershed. The effects of fire on hydrological losses were modeled by adjusting the CN values for different fire severities. Direct infiltration measurements were carried out to better understand the effect of fire on soil infiltration capacity. We simulated the hydrological response of the burned watershed following one of the most severe storm events that had hit the area in the last few years. Fire had serious repercussions in regard to the hydrological response, increasing the flood peak and the runoff volume up to 125% and 75%, respectively. Soil infiltration capacity was seriously compromised by fire as well, reducing unsaturated hydraulic conductivity up to 75% compared with pre-fire conditions. These findings can provide insights into the impact of forest fires on the hydrological response of a whole watershed and improve the assessment of surface runoff alterations suffered by a watershed in post-fire conditions.