Pepper (Capsicum annuum) is a globally important vegetable, and Verticillium wilt is an important disease affecting peppers and is caused by Verticillium dahliae, which can severely reduce yields. However, the molecular mechanisms underlying the responses of pepper to infection by V. dahliae are largely unknown. We performed physiological and transcriptome analysis using resistant and susceptible pepper cultivars inoculated with V. dahliae. Compared to the susceptible cultivar MS66, the resistant cultivar MS72 retained higher chlorophyll content and lower malondialdehyde content after inoculation. At 3 days after inoculation (DAI), compared with MS66, 534 differentially expressed genes (DEGs) were identified in MS72. At 5 DAI, 2392 DEGs were identified in MS72 compared with MS66. The DEGs in MS72 were mainly enriched in the cell wall and photosynthesis-related Gene Ontology terms, as well as in pathways such as cutin, suberin, wax biosynthesis, phenylpropanoid biosynthesis, and photosynthesis. Using weighted gene co-expression network analysis, 36 hub genes involved in the resistance response were identified, including the transcription factor bHLH93 (Capana04g000815), defense-like protein 1 (MSTRG.5904), and miraculin-like (Capana10g002167). Our findings contribute to a more comprehensive understanding of the response mechanism of pepper to V. dahliae inoculation, providing new avenues for improving pepper resistance through breeding programs.