Apple scab, caused by the fungal pathogen Venturia inaequalis is among the most prevalent and economically important diseases in commercial apple orchards in regions with temperate climates worldwide. The absence of durable apple scab resistance in the majority of commercially desired cultivars often mandates numerous fungicide applications each season to successfully manage the disease. Highly effective single-site fungicides have enhanced the ability to manage a number of phytopathogenic fungi, including V. inaequalis. Unfortunately the highly specific nature and repetitive use of these fungicides has led to their diminished efficacy and widespread resistance in V. inaequalis. The identification of the prevalence of single-site resistance in populations of V. inaequalis and an understanding of molecular mechanisms of resistance to these fungicides can aid in the rapid detection of fungicide resistance, the deployment of fungicide anti-resistance management strategies, and the development of efficient and effective chemical management programs for apple scab control. In this dissertation, a combination of applied and basic research was implemented to gain further understanding of the molecular mechanisms associated with practical resistance to DMI and QoI fungicides in isolates and/or populations of V. inaequalis. Microscopy-aided mycelial growth assays were used to determine sensitivity phenotypes to the DMI fungicides myclobutanil and difenoconazole and to the QoI fungicide trifloxystrobin. The majority of populations of V. inaequalis collected throughout the Northeastern, Mid-Atlantic, and Mid-Western United States were found to have reduced sensitivity or practical resistance to myclobutanil, but not difenoconazole. Illumina sequencing and reverse-transcriptase quantitative PCR were used to identify the contribution of target gene overexpression and the presence of upstream repeated elements in myclobutanil and difenoconazole resistance. Another molecular technique, allelespecific quantitative PCR was used to evaluate the role of target gene heteroplasmy in the quantitative resistance response and practical resistance to trifloxystrobin in isolates and populations of V. inaequalis. Additionally, baseline sensitivity of V. inaequalis to three SDHI fungicides was determined, and the sdhB gene, a target for SDHI fungicides, was identified and characterized. In summary, the results of this dissertation contribute to the identification and understanding of mechanisms associated with single-site fungicide resistance in V. inaequalis.