Cucumber mosaic virus (CMV) poses a considerable threat to a diverse array of crops in global agriculture. CMV impacts commercially important cut lilies by diminishing both yield and flower quality. We used RNA sequencing (RNA-seq) to investigate the changes in gene expression in the leaves and bulbs of four distinct cultivars of cut lily, ‘Cancun,’ ‘Brunello,’ ‘Connecticut King,’ and ‘Casa Blanca’ following CMV infection. Notably, CMV affected photosynthetic processes by significantly downregulating genes associated with photosynthesis. In addition, CMV infection was detrimental to chloroplast function and energy production. We observed differential expression of genes associated with both dominant and recessive resistance pathways that are crucial for preventing virus entry, replication, and systemic spread within the plant. Based on functional annotation and differential gene expression analysis, we identified the regulatory genes involved in triggering immune responses, modulating signal transduction, and specific host factors during CMV infection. To validate the RNA-seq findings, we selected four genes involved in resistance, virus multiplication, and virus spread and analyzed them using real-time quantitative reverse transcription PCR (qRT-PCR) with specific primers. The qRT-PCR results aligned closely with those from RNA-seq, showing consistent fold-change responses for the genes that were differentially expressed, indicating that the RNA-seq results were reliable. These results deepen our understanding of the complex genetics behind plant-virus interactions while also providing information for breeding programs that aim to develop CMV-resistant lily cultivars.