Northern corn leaf blight (NCLB) is one of the most important diseases of corn in the Americas due to potential yield losses. Agronomic practices such as no-tillage, double-cropping or late-planted corn, and use of susceptible hybrids may compromise corn productivity whenever NCLB is present; therefore, fungicide applications may restore productivity by lowering NCLB damage. Hence, the goal of this work was to assess the value of Nativo fungicide applications at different corn growth stages using hybrids of different NCLB resistance levels across a wide range of disease pressure environments. To achieve this goal, field experiments were planted in a total of 26 locations during a 3-year period in Argentina and Paraguay, aiming for environments with high NCLB pressure. The results indicate that Nativo fungicide applications increase yield by lowering the rate of NCLB severity increase with time. The proper time for applying was at the onset of disease (less than 2% in severity, commonly at V10-V14 growth stages), although this onset period may vary with the weather and it was usually sooner in susceptible hybrids. Nativo Fungicide applications provide the most value on hybrids with intermediate levels of susceptibility, in which well-timed fungicide applications can achieve a similar yield than resistant hybrids without fungicide applications. However, in hybrids too susceptible for the environment, Nativo fungicide applications may not help matching the yield when compared to the best hybrids for the environment. As a summary, fungicide applications can be a valuable tool to manage NCLB, in which proper scouting throughout vegetative and early reproductive stages for NCLB damage, together with forecasts to predict weather conducive for disease, will allow informed decision-making for applying at the right time, maximizing economic benefits.