Fusarium solani-induced quality deterioration in stored sweet potato is poorly characterized and understood. This study examined the effects of F. solani infection in Xinxiang sweet potato roots during storage. The results showed that while there were no external symptoms following F. solani infection, upon cutting the roots, the cut surface of the infected root rapidly turned black, whereas the untreated control roots remained unaffected. The metabolites and transcriptive differences between F. solani-infected and control sweet potato roots were investigated with high-performance liquid chromatography, metabolomic analysis, and an Illumina Novaseq platform. The results showed that levels of the toxic ipomeamarone accumulated as high as 2.36 mg/kg DW in tissue after F. solani inoculation and 6 days storage at 28 °C, where the control tissue sample did not accumulate any ipomeamarone. Metabolomic analysis showed that isochlorogenic acid and l-tyrosine significantly increased in the infected tissue and associated with the darkening cut surface of the infected sweet potato. In transcriptomic analysis, a total of 13, 14, and 6 key genes in ipomeamarone, isochlorogenic acid, and l-tyrosine biosynthesis pathways, respectively, were identified. A conceptual model elucidating the physiological and molecular mechanism of F. solani-induced quality deterioration in sweet potato is proposed.