The hybrid configuration of bio-reinforced composites has established a new extended boundary for the development of pro-ecological technologies due to light weight, moderate specific strength, low cost, environmental benefits, and potential applications of natural components. This work investigates the physical and mechanical properties of hybrid composites made of sisal/glass fibres and Portland cement inclusions. A full factorial design was generated to identify the effects of the stacking sequence and cement particles on the flexural strength, flexural stiffness, apparent density, apparent porosity and water absorption of the composites. The significant contributions of these main factors and their interactions were determined via Design of Experiments (DoE) and Analysis of Variance (ANOVA). The fracture features and damage mechanisms of hybrid composite were also reported. The inclusion of cement microparticles led to an increased apparent porosity, as well as enhanced water absorption, flexural stiffness and flexural strength of the hybrid composites. The mechanical properties were strongly dependent on the fibre stacking sequence, which accounts for approximately 98% of the effects observed. Moreover, the stacking sequence affected the damage mechanism of the bio-composites. Finally, the replacement of glass fibres by unidirectional sisal reinforcements may potentially improve the specific properties in structural applications with an environmental sustainable footprint.