Ceratocystis fimbriataEllis & Halsted is the pathogen causing black rot in sweet potatoes that can lead to flavor change and toxin release. This study detected the volatile organic compounds (VOCs) ofC. fimbriata-infected sweet potatoes in the early stages using headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS). A total of 55 VOCs were identified, including aldehydes, alcohols, esters, ketones, and others. The content of aldehydes and ketones showed a decreasing trend, while alcohols and esters showed an increasing trend. An increase in infection time elevated the content of malondialdehyde (MDA) and pyruvate, while the starch content decreased, the content of soluble protein initially increased, then decreased, and the activities of lipoxygenase (LOX), pyruvate decarboxylase (PDC), alcohol dehydrogenase (ADH), and phenylalanine ammonia-lyase (PAL) increased. The changes in VOCs were closely related to the content of MDA, starch, pyruvate, and the activities of LOX, PDC, ADH, and PAL. Sweet potatoes showed a good discrimination effect by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) from 0 to 72 h. Twenty-five differential VOCs could be used as early-stage characteristic compounds ofC. fimbriata-infected sweet potatoes for early disease monitoring.