The grapevine syndrome, Esca proper, causes significant yield losses. This study analyses and discusses the enological traits of musts from healthy (HV) and Esca-proper-affected (EpV) ‘Primitivo’ vines cropped in southern Italy. Tiger-striped leaves, sudden wilting on arms or shoots, berry spots, shrivelling and wilting, wood browning and white rot are linked to the presence of Phaeoacremonium minimum, Phaeomoniella chlamydospora, and Fomitiporia mediterranea within the woody tissues and characterize EpVs. The lack of symptoms on trunks, leaves, berries, and in the wood of branches and shoots, along with the absence of Esca-proper mycota, typifies HVs. Must from the selected HVs is darker and contains greater total soluble solids, reducing sugars, titratable and volatile acidity, tartaric, citric, and L-malic acid, and total polyphenols. The must from the selected EpVs has a higher pH and laccase activity, and contains pullulan, scytalone, and isosclerone, secondary metabolites of P. minimum and P. chlamydospora. During fermentation, musts from EpVs negatively impact the growth and enological performance of Saccharomyces cerevisiae Byosal HS1™ and IOC 18-2007™ and reduce the overall quality of the resulting wines. The physical–chemical conditions during fermentation may degrade pullulan and aid scytalone oxidation to isosclerone.