For two consecutive growing seasons (2017 and 2018), three different fungicide spray programs, each with five sprays from unrelated chemical groups, were evaluated for their effectiveness against apple scab (causal agent: Venturia inaequalis) in an experimental trial in Greece. The targeted application programs consisted of five sprays with protective and systemic fungicides from unrelated chemical groups, in alternation. The applications were started at the pink bud stage (a copper-based fungicide had previously been applied at the green bud stage) and completed at the second fruit fall to arrest the primary infections by ascospores. These five-spray programs were compared to the standard farmer practice (12 sprays per season), whereas untreated plots were used as controls. The timing of the applications was based: a) on the critical growth stage of the crop, and b) on the risk analysis for infection calculated by the software Field Climate, which incorporated meteorological data from the trial site. All the five-spray programs were of very high efficacy against apple scab, showing disease severity ratings on leaves and fruits below 1.88%. In both years, in the untreated control, the disease incidence and severity on leaves ranged from 96.5% to 99.3% and from 65.2% to 75.93%, respectively. The five-spray programs showed similar efficacy to the standard 12-application program in all cases. From the results, it becomes apparent that apple scab can be controlled effectively by five targeted applications with selected fungicides at critical growth stages of the crop.