A decision support system (DSS) involving an approach for predicting wheat leaf rust (WLR) infection and progress based on night weather variables (i.e., air temperature, relative humidity, and rainfall) and a mechanistic model for leaf emergence and development simulation (i.e., PROCULTURE) was tested in order to schedule fungicide time spray for controlling leaf rust progress in wheat fields. Experiments including a single fungicide treatment based upon the DSS along with double and triple treatment were carried out over the 2007-2009 cropping seasons in four representative Luxembourgish wheat field locations. The study showed that the WLR occurrences and severities differed according to the site, cultivar, and year. We also found out that the single fungicide treatment based on the DSS allowed a good protection of the three upper leaves of susceptible cultivars in fields with predominant WLR occurrences. The harvested grain yield was not significantly different from that of the double and triple fungicide-treated plots (P < 0.05). Such results could serve as basis or be coupled to cost-effective and environmentally friendly crop management systems in operational context.