To support the inefficient limitation of long-term biosystem by well-known simultaneous saccharification and fermentation (SSF), electron beam irradiated rice straw (at 80 kGy, 1 MeV, and 0.12 mA) was fermented using fungal-based simultaneous saccharification and fermentation (FBSSF) by saprophytic zygomycetes Mucor indicus. Based on the growth optimization (by response surface methodology), this eco-friendly bioprocess either without metabolic inhibitors (especially furfurals and acetic acids) or byproducts (especially glycerols) significantly increased the biodegradability and fermentability of lignocellulosic rice straw. Specifically, when irradiated straw was simultaneously bioconverted by M. indicus for 48 h, the ethanol yield was 57.2% of the theoretical maximum. This value was on the similar level as the 59.8% (for 144 h) measured from processed straw by well-known SSF. Furthermore, after FBSSF for 144 h based on large-scale mass balance, the ethanol concentration and production yield, and productivity were 34.6 g/L, 72.3% of the theoretical maximum, and 0.24 g/L/h, respectively.