The performance of polymer composites strongly depends upon the constituents and the processing method of composite fabrication. The present study investigates the effect of fabrication processes (hand lay-up process, compression molding and resin transfer molding (RTM)) on the physical and mechanical properties of the developed bio-composites having different combinations of uni-directional sisal and uni-directional ramie fiber mat reinforcement in unsaturated polyester matrix. Scanning electron micrographs (SEM) were used to study the failure behavior of composite constituents under various loading conditions. Results indicate that composites fabricated by RTM process showed 5%–15% voids (percentage density change) while hand lay-up showed 30%–45% voids (percentage density change). Longitudinal and transverse flexural modulus of composites fabricated by RTM and compression molding are 2–3 times higher than composites developed by hand lay-up process. The study concludes that processing of composites through different routes and varying the reinforcement have significant effect on mechanical properties of the developed bio-composites.