Bio-based materials are becoming increasingly important as demand for conventional wood-based products raises environmental issues, potentially leading to deforestation. As a result, environmentally acceptable, cost-effective, and easily available alternative natural biomass materials for these intended utilizes are highly required. In this work, a waste wheat straw cellulose polymer matrix composite reinforced with sisal fiber through physical and chemical treatment methods for fiberboard application was synthesized and characterized. The composite materials were developed using the polymer solution casting method. Waste wheat straw composites with 0, 5, 10, 15, 20, 25, and 30 wt% of sisal fiber with respect to the matrix were prepared. Qualitative and quantitative approaches, as well as exploratory and experimental research methods, were employed. Fourier transform infrared (FTIR) spectroscopy was used to investigate the functional group of wheat straw cellulose, while scanning electron microscopy (SEM) was used to examine the sisal fiber morphology. Flexural strength was tested by using a universal testing machine, and impact strengths were measured by a V-notch Charpy tester based on medium-density fiberboard (MDF) and low-density fiberboard (LDF) as control samples. The water absorption of the samples was also studied. The work complied with ANSI A208.2–2002's general test standards for general usage. The results showed that the maximum flexural strength attained at 20 wt% of reinforcement was (56.83 MPa) and the impact strength at 20 wt% sisal fiber was (30.33 J), while the MDF and LDF control samples' flexural strengths were 35.5 MPa and 41.5 MPa, respectively, and the impact strengths were (20.16 J and 25 J), respectively. The lowest water absorption value was achieved at 5 wt% of sisal fiber, and the value was (2.09%). However, water absorption of (74.04%) for MDF and (106.98%) for LDF was measured. Thus, it was discovered that using waste biomass such as wheat straw instead of raw wood may provide a composite material with superior flexural strength, impact strength, and reduced water absorption for fiberboard applications.