Poly(3-hydroxybutyrate) (PHB) belongs to a class of polyhydroxyalkanoates that are synthesized by prokaryotic microbes and serve as intracellular carbon and energy storage compounds. PHB-based plastics offer several advantages over conventional petroleum-based synthetic plastics, like biodegradability, renewability and low carbon footprints among others, thus promulgating a biobased market from niche to high volume applications. Considerable industrial interests exist in PHB; their cost of production is a major limiting factor. The present work focuses on the development of an economically viable glycerol-based method for PHB production, drawing on statistical and mechanistic models. An enhanced growth-associated PHB content of 40% (wt/wt) and cell biomass of 1.35 g/L were obtained at a glycerol concentration of 40 g/L in the model guided constant fed-batch strategy. This study facilitates an alternative bioprocess for sustainable production of high-value bioplastics.