Natural fibers are among the most employed reinforcements in the manufacturing process of innovative fiber-based composite materials. As with any composite materials, the properties of composites depend on the type and properties of the fiber, fiber structure, composition (hybridization), and treatment. In this study, the composite was fabricated by using hand lay-up with 100/0, 75/25, 50/50, 25/75, and 0/100 Enset/Sisal (E/S) hybridization ratio. Three cases, i.e., untreated, 5%, and 10% NaOH treatment were considered. The effects of hybridization and treatment on the mechanical and water absorption properties of woven and unidirectional orientation of E/S hybrid composite were evaluated by using a two-factors analysis of variance. The fiber–matrix interfacial fractured surface was characterized by scanning electron microscopy. The treated (5% NaOH) and woven fiber orientation exhibited better mechanical properties than untreated and unidirectional hybrid composites. The flexural and tensile strength of the woven composite was improved by 5% and 9%, respectively, when compared with woven untreated 50/50 volume ratio of composites. In both samples and orientations, the hybridization effects show a higher percentage contribution to the mechanical properties. But, in both orientations of composite samples, the treatment effects show a higher percentage contribution for water absorption properties.