Recently, leaf spot disease caused by Phaeophleospora spp. fungi has become a severe problem in eucalyptus clonal plantations. These pathogens can kill Eucalyptus trees, and cases can be found in different stages of tree development, ranging from seedlings in nurseries to trees in the field. Before deploying a large-scale Eucalyptus clonal plantation, selecting clones resistance to disease is important in addition to selecting for optimal growth and wood properties. In this research, we explored anatomical and chemical leaf characteristics associated with potential leaf spot disease resistance. The study was conducted on a 6-mo-old eucalypt clonal plantation at a forestry company in South Sumatra, Indonesia. Three selected clones, i.e., clones 79 and 80 (E. pellita × E. brassiana), and clone 47 (pure E. pellita), were assessed for their growth, severity of spontaneously occurring disease, and leaf characteristics (the stomatal density, stomatal size, thickness of adaxial and abaxial palisade mesophyll, and phenol contents). Clone 79 was susceptible, while clones 47 and 80 were more resistant to the disease. The stomatal size and density and leaf phenol contents assessed from healthy clones were not good indicators for determining resistant clones. The thickness of the abaxial palisade parenchyma, however, was negatively correlated with disease severity. Comparing palisade mesophyll thickness is suggested to be a quick, simple, and cheap approach for a preliminary assessment of potential resistance against leaf spot disease among different Eucalyptus clones.