Background <p>This study explores a sustainable method for biofuel production from leather tanning waste (LTW) using a novel single-step, catalyst-free supercritical methanolysis (SpCM) process. Traditional biodiesel production methods often require catalysts and involve complex purification steps, whereas this study aims to optimize process parameters to enhance biodiesel yield while reducing energy and material consumption.</p> Methods <p>The research employed a Box–Behnken experimental design integrated with response surface modeling (RSM) to optimize key process variables, including alcohol-to-LTW molar ratio (<i>r</i>_mo), operating temperature, pressure, and reaction duration. The produced biodiesel was characterized according to EN 14214 standards. Kinetic studies of the transesterification reaction were conducted, and a robust reactor model was developed in Aspen Plus to estimate the kinetic parameters.</p> Results <p>The activation energy (<i>E</i>_a) and pre-exponential factor (<i>A</i>) were determined to be 45.085&#xa0;kJ/mol and 86.24&#xa0;s⁻¹, respectively, with a rate constant (<i>k</i>) of 0.0098&#xa0;s⁻¹ at an optimized temperature of 322.938&#xa0;°C. The optimized conditions using RSM achieved a biodiesel yield of 89.35% at an <i>r</i>_mo of 32.35:1, a temperature of 322.938&#xa0;°C, a pressure of 219.073&#xa0;bar, and a reaction time of 14.26&#xa0;min. The simulation model under the same conditions predicted a biodiesel yield of 89.49%, demonstrating excellent agreement with experimental results, with a maximum error of 0.54%.</p> Conclusions <p>This study presents a comprehensive approach to biodiesel production from LTW, demonstrating an efficient and sustainable alternative to conventional methods. The optimized catalyst-free SpCM process minimizes energy input and material usage while achieving high biodiesel yields. These findings contribute to waste valorization in the leather industry and support environmental sustainability efforts.</p> Graphical abstract <p></p>