<p>Rising global energy demand coupled with the severe environmental/climatic impact of exorbitant usage of fossil fuels and consequent rapid depletion of their finite reserves, highlights the urgent need for sustainable and eco-friendly alternatives. Among various alternatives of renewable energy, bioenergy from abundantly available lignocellulosic biomass has emerged as one of the most potent and sustainable resource which not only promises generation of clean energy but ensures waste valorisation. Current study explores the next generation bioprocessing of sesame stalk biomass as a potential feedstock for bioethanol production using the protic ionic liquid (PIL) triethylammonium hydrogen sulfate ([TEA][HSO₄]) in combination with zinc chloride as the pretreatment approach for the first time. This was followed by saccharification of pretreated biomass with a PIL-tolerant cellulase/xylanase preparation produced from a newly isolated fungus <i>Talaromyces adpressus</i> AT12. Process parameters for pretreatment and enzymatic saccharification were optimized via Design of Experiments, leading to a 2.58-fold (126.06 to 325.29&#xa0;mg/g biomass) increase in reducing sugar yield. The liberated sugars were efficiently fermented to ethanol, producing 151.85&#xa0;mg ethanol/g biomass. Structural and chemical analyses (SEM, FTIR, XRD) of pretreated biomass confirmed the extensive surface disruption, enhanced porosity and swelling with selective removal of lignin and hemicelluloses, and increased cellulose crystallinity, demonstrating improved biomass digestibility. These findings highlight the efficacy of integrated PIL-based pretreatment and enzymatic saccharification as a sustainable strategy for valorizing agricultural residues into biofuels. Further studies on deeper understanding of the underlying functional mechanisms of PIL-based pretreatment may facilitate the development of tailored and high-efficiency strategies for improved biomass conversion to biofuel.</p> Graphical abstract <p></p>