Synthetic fungicides with a single site of action are generally more prone to encounter resistance by fungal pathogens than their multi-site counterparts. Early identification of target mutations in response to continued use of similar material is critical to the longevity of fungicide tools. A suite of 14 foliar Podosphaera clandestina isolates representing various growing regions of the Pacific Northwest (PNW) was subjected to high throughput Illumina sequencing. The ITS sequences from all isolates confirmed the identity of P. clandestina, incitant of sweet cherry powdery mildew. The data were used to identify the fungicide target genes, Cytochrome b (COB, FRAC 11) and, CYP/ ERG11 (FRAC 3). The deduced amino acid sequences from the Illumina contigs were screened for the presence of target mutations. The results indicated the presence of COB target mutation at position 143 (G143A/R) in samples across PNW. But, no target mutations were found for CYP/ ERG11 gene in all of the samples analyzed. A pilot-scale bioassay on one of the isolates using eight fungicides revealed resistance to three different FRAC groups. Overall, studies confirmed that the fungicide resistance is factual and more information is needed to strategically address this situation. The information from such studies will likely avoid a widespread problem of fungicide resistance and poor management of powdery mildew on cherries. Additionally, replacing compromised fungicides with newer chemistries offers better disease management and promotes the economic sustainability of the cherry orchards across the PNW.