Microbial proteases due to their huge application potential have attracted considerable research attention and account for more than 60% of the worldwide enzyme sales. However, large-scale industrial application of proteases is hindered due to their poor performance under relatively hostile industrial conditions (extremes of temperature, pH) and the high production cost. In the current study, the production of a thermostable and wide-range pH stable protease was accomplished from a newly isolated Bacillus subtilis K-1 strain using cost-effective agricultural residues. Process optimization for protease production was conducted by employing one-variable-at-a-time and statistical approaches. The most significant variables for protease production were identified as incubation time, soybean meal, mustard cake, and wheat bran. Optimization of these variables by central composite design of response surface methodology resulted in a substantial protease yield enhancement (112%). Exploitation of agricultural wastes as substrates may pave the way for cost-effective production of protease with industrially desirable attributes.