In apple (Malus domestica), the polyphenol profile is dominated by phloridzin, but its physiological role remains largely elusive. Here, we used MdUGT88F1 (a key UDP-glucose:phloretin 2'-O-glucosyltransferase gene) transgenic apple lines and Malus spp. germplasm to gain more insight into the physiological role of phloridzin in apple. Decreasing phloridzin biosynthesis in apple lines by RNA silencing of MdUGT88F1 led to a series of severe phenotypic changes that included severe stunting, reduced internode length, spindly leaf shape, increased stem numbers, and weak adventitious roots. These changes were associated directly with reduced lignin levels and disorders in cell wall polysaccharides. Moreover, compact organization of tissues and thickened bark enhanced resistance to Valsa canker (caused by the fungus Valsa mali), which was associated with lignin-and cell wall polysaccharide-mediated increases of salicylic acid and reactive oxygen species. Phloridzin was also assumed to be utilized directly as a sugar alternative and a toxin accelerator by V. mali in apple. Therefore, after infection with V. mali, a higher level of phloridzin slightly compromised resistance to Valsa canker in MdUGT88F1-overexpressing apple lines. Taken together, our results shed light on the importance of MdUGT88F1-mediated biosynthesis of phloridzin in the interplay between plant development and pathogen resistance in apple trees.