This study presents mechanistic investigations in ultrasound-assisted bioethanol fermentation using Parthenium hysterophorus biomass. Ultrasound (35 kHz, 10% duty cycle) has been used for sonication. Experimental results were fitted to mathematical model; the kinetic and physiological parameters in the model were obtained using Genetic Algorithm (GA) based optimization. In control experiments (mechanical shaking), maximum ethanol titer of 10.93 g/L and cell mass concentration of 5.26 g/L was obtained after 18 h. In test experiments (mechanical shaking and intermittent sonication), ethanol titer of 12.14 g/L and cell mass concentration of 5.7 g/L was obtained in 10 h. This indicated similar to 2x enhanced productivity of ethanol and cell mass with sonication. Trends in model parameters obtained after fitting of model to experimental data essentially revealed that beneficial influence of ultrasound on fermentation is a manifestation of enhanced trans-membrane transportation and dilution of toxic substances due to strong micro-convection induced by ultrasound. (C) 2014 Elsevier Ltd. All rights reserved.